Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis
Open accessAbstract
CONTEXT: Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. OBJECTIVES: Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone. DESIGN: Bi-directional Mendelian randomization (MR) analysis on prospective cohorts. SETTING: Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden). PARTICIPANTS: 7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs. MAIN OUTCOME MEASURES: BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site. RESULTS: 1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum testosterone. No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349). CONCLUSIONS: Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men.
AI snapshot
Written from the paper’s full text.
TL;DR
In a bi-directional Mendelian randomization analysis of 7,446 Caucasian men, genetically instrumented higher BMI causally lowered serum testosterone, while genetically instrumented testosterone did not affect BMI. The authors conclude that reducing BMI is expected to increase serum testosterone in men.
Key findings
- A 1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42 to -0.09, p = 2.8×10⁻³); the unweighted score gave -0.29 SD (95% CI: -0.48 to -0.10, p = 2.5×10⁻³).
- For a BMI reduction from 30 to 25 kg/m², the estimated effect was a 13% increase in serum testosterone using the weighted BMI score and 15% using the unweighted score; the corresponding observational estimate was 16%.
- No association was seen for genetically instrumented testosterone with BMI; this was confirmed using large-scale data from the GIANT consortium (n = 104,349).
- The observational association was also significant: 1 SD increase in ln-transformed BMI was associated with a 0.30 SD decrease in serum testosterone (95% CI: -0.35 to -0.24) in random-effects meta-analysis.
Methods
- Bi-directional Mendelian randomization analysis using five cohorts from Denmark, Germany, and Sweden (Inter99, SHIP, SHIP Trend, GOOD, and MrOS Sweden), including 7,446 Caucasian men with genotype and phenotype data.
- Genetic instruments were a weighted genetic risk score based on 97 BMI-associated SNPs and a weighted testosterone-decreasing score based on three testosterone-associated SNPs (rs6258, rs12150660, rs5934505); unweighted scores were also used.
- Main analysis used the IV ratio method with two-stage least squares regression to estimate causal effects of BMI on serum testosterone and vice versa, with adjustment for age, smoking, site, and time of blood sampling where applicable.
Limitations
- The paper states that participants were unrelated men of European ancestry, limiting generalizability to other ethnic groups.
- The paper states that the mechanism for the causal effect of BMI on serum testosterone cannot be determined and may involve the hypothalamus-pituitary-gonadal axis.
- The paper states that genetic markers do not examine effects from extremes of non-linear distributions, so a possible causative effect of severe testosterone deficiency on BMI cannot be discounted.
- The paper notes a small overlap (<2%) between its cohorts and the BMI GWAS used to weight SNPs, which could bias the weighted score, though similar results with unweighted and FTO-only scores made this unlikely.
- The paper states that the close connection between testosterone and SHBG makes it difficult to discriminate between a direct effect on serum testosterone and an effect mediated via SHBG.
- Evident from the text: the MR approach relies on assumptions of no pleiotropy and no confounding, which the authors tested where possible but cannot fully exclude.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 44 cited sources checked · 0 supported · 0 flagged
- Findingown data
There was evidence of heterogeneity among cohorts in the meta-analysis (I-squared = 82%, p = 0.0005).
“we found evidence of heterogeneity (I-squared = 82%, p = 0.0005) among cohorts”
Quote in the paperNot a substantial claim - Findingown data
The observational association was more pronounced in the MrOS cohort (oldest men, mean age 75.4 years; -0.35 SD testosterone per SD ln BMI) compared to the GOOD cohort (youngest men, mean age 18.9 years; -0.20 SD testosterone per SD ln BMI).
“but slightly more pronounced in the MrOS cohort including the oldest men (mean age 75.4 years; -0.35 SD T per SD ln BMI) compared to the GOOD cohort including the youngest men (mean age 18.9 years; -0.20 SD T per SD ln BMI; Fig 1).”
Quote in the paperNot a substantial claim - Findingown data
In pooled analysis, a 1 SD increase in ln-transformed BMI was associated with a 0.30 SD decrease in serum testosterone (95% CI -0.33--0.28).
“revealing that 1 SD increase in ln-transformed BMI was associated with 0.30 SD decrease in serum T (95% CI: -0.33–-0.28).”
Quote in the paperNot a substantial claim - Findingown data
In random effect inverse-variance meta-analysis, a 1 SD increase in ln-transformed BMI was associated with a 0.30 SD decrease in serum testosterone (95% CI -0.35--0.24).
“demonstrating that a 1 SD increase in ln-transformed BMI was associated with a 0.30 SD decrease in serum T (95% CI -0.35–-0.24; Fig 1).”
Quote in the paperNot a substantial claim - Findingown data
The genetic risk scores wGRSBMI, uwGRSBMI, wGRST and uwGRST were not associated with age and smoking (p>0.05).
“the different GRSs evaluated in the present study (wGRSBMI, uwGRSBMI, wGRST and uwGRST) were not associated with these two potential confounders (p>0.05; S1 Fig).”
Quote in the paperSubstantial claim
- Findingown data
The observational association between BMI and serum testosterone was significant in all cohorts after adjustment for age, smoking, site and blood sampling time.
“The observational association between BMI and serum T was significant in all cohorts after adjustment for age, smoking, site and blood sampling time”
Quote in the paperNot a substantial claim - Findingown data
There was no evidence of heterogeneity in the BMI SNP analyses.
“There was no evidence of heterogeneity in these analyses.”
Quote in the paperNot a substantial claim - Findingown data
None of the SNPs were still significant after adjustment for BMI.
“However, none of the SNPs were still significant after adjustment for BMI.”
Quote in the paperSubstantial claim - Findingown data
There was no significant difference between β-coefficients from observational and IV analysis (wGRSBMI p=0.44, uwGRSBMI p=0.82).
“There was no significant difference between β-coefficients from observational and IV analysis (wGRSBMI: p value 0.44, uwGRSBMI: p value 0.82).”
Quote in the paperSubstantial claim - Findingown data
wGRST was robustly associated with serum SHBG (combined cohort p=2.7*10−49).
“wGRST was robustly associated with serum SHBG (combined cohort: p = 2.7*10−49, S3 Fig).”
Quote in the paperSubstantial claim - Findingown data
IV ratio analyses provided no evidence for a causal effect of serum testosterone on BMI.
“Furthermore, the IV ratio analyses provided no evidence for a causal effect of serum T on BMI (Table 2, S3 Table).”
Quote in the paperSubstantial claim - Findingown data
The association between wGRSBMI and serum testosterone remained significant (p=0.02) after adjustment for serum SHBG in the pooled combined cohort.
“Interestingly, the association between wGRSBMI and serum T remained significant (p = 0.02) after adjustment for serum SHBG in the pooled combined cohort.”
Quote in the paperSubstantial claim - Findingown data
After adjustment for BMI, none of the wGRSBMI or uwGRSBMI associations with serum testosterone were still significant.
“After adjustment for BMI, none of these associations were still significant.”
Quote in the paperSubstantial claim - Findingown data
No evidence of non-linearity was found for wGRST or uwGRST.
“No evidence of non-linearity was found for wGRST or uwGRST.”
Quote in the paperNot a substantial claim - Findingown data
All three SNPs included in wGRST were individually associated with serum testosterone (p<0.05/3).
“All three SNPs included in the wGRST were individually associated with serum T (p<0.05/3; S4 Table).”
Quote in the paperSubstantial claim - Findingown data
In the GIANT consortium (up to 104349 men), no significant evidence was found that any of the two autosomal testosterone SNPs were associated with BMI individually or combined as a genetic risk score.
“For the two autosomal SNPs it was possible to use the GIANT consortium, including up to 104349 men, to evaluate the causal effect of serum T on BMI in a larger setting. However, no significant evidence was found supporting that any of these T SNPs were associated with BMI individually, or when combined as a genetic risk score (S6 Table).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [17] AE Locke, 2015, Genetic studies of body mass index yield new insights for obesity biology, Nature source
Not checked in the free run.
- cites [28] KS Vimaleswaran, 2013, Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts, PLoS medicine source
Not checked in the free run.
- Findingown data
IV analyses revealed that 1 SD increase in ln-transformed BMI lead to a 0.25 (wGRSBMI, p=2.8*10−3) to 0.29 (uwGRSBMI, p=2.5*10−3) SD decrease in serum testosterone.
“IV analyses used to establish the direction and causality of the BMI-T association, revealed that 1 SD increase in ln-transformed BMI lead to a 0.25 (using wGRSBMI, p = 2.8*10−3) to 0.29 (using uwGRSBMI, p = 2.5*10−3) SD decrease in serum T (Table 2, S1 Table).”
Quote in the paperSubstantial claim - Findingown data
Each SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone.
“Each SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum T.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The genotypes are randomized.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- The authors state this as an assumption: The genotype is independent of confounders.
- Findingown data
Both wGRSBMI and uwGRSBMI were significantly and inversely associated with serum testosterone in the meta-analyzed combined cohort (p=2.0*10−3 and p=1.7*10−3).
“Both wGRSBMI (p = 2.0*10−3) and uwGRSBMI (p = 1.7*10−3) were significantly and inversely associated with serum T in the meta-analyzed combined cohort (Fig 2C; S1 Table).”
Quote in the paperSubstantial claim - Findingown data
The wGRSBMI and uwGRSBMI associations with BMI did not vary by age, smoking or serum testosterone (p>0.05 for all interaction terms).
“The wGRSBMI and uwGRSBMI associations with BMI did not vary by age, smoking or serum T (p > 0.05 for all interaction terms in pooled analyses).”
Quote in the paperSubstantial claim - Findingown data
No evidence of non-linearity was found for wGRSBMI or uwGRSBMI.
“No evidence of non-linearity was found for wGRSBMI or uwGRSBMI.”
Quote in the paperNot a substantial claim - Findingown data
wGRSBMI was inversely associated with serum SHBG in the pooled combined cohort.
“wGRSBMI was inversely associated with serum SHBG in the pooled combined cohort (S3 Fig).”
Quote in the paperNot a substantial claim - Findingown data
There was no evidence of heterogeneity in the testosterone SNP analyses.
“There was no evidence of heterogeneity in these analyses (Fig 2B).”
Quote in the paperNot a substantial claim - Findingown data
After adjustment for serum testosterone, wGRSBMI was not significantly associated with SHBG (combined cohort p=0.59).
“However, after adjustment for serum T wGRSBMI was not significantly associated with SHBG (combined cohort: p = 0.59).”
Quote in the paperSubstantial claim - Findingown data
Our analyses provided no evidence for a causal role of serum testosterone on BMI.
“Our analyses provided no evidence for a causal role of serum T on BMI.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The genotypes are randomized.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- The authors state this as an assumption: The genotype is independent of confounders.
- Findingown data
In the opposite analysis where serum testosterone was the outcome and SHBG the covariate, wGRSBMI was significantly associated with serum testosterone.
“However, in the opposite analysis where serum T was the outcome and SHBG the covariate, wGRSBMI was significantly associated with serum T, supporting a SHBG-independent effect of BMI on serum T.”
Quote in the paperSubstantial claim - Findingown data
The BMI-based genetic risk score was associated with serum SHBG.
“In the present study, we found evidence of a causal effect of BMI on serum T, but the BMI-based genetic risk score was also associated with serum SHBG.”
Quote in the paperSubstantial claim - Findingown data
The use of the GIANT consortium to test the association between testosterone-related autosomal SNPs and BMI in a much larger sample including 104,349 men also failed to identify a causal role of testosterone on BMI.
“However, the use of the GIANT consortium to test the association between T-related autosomal SNPs and BMI in a much larger sample including 104349 men also failed to identify a causal role of T on BMI.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The genotypes are randomized.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- The authors state this as an assumption: The genotype is independent of confounders.
- Findingown data
When serum testosterone was added as a covariate, the association between the BMI-based genetic risk scores and SHBG was no longer significant.
“When serum T was added as a covariate to the analysis, the association between the BMI-based genetic risk scores and SHBG was no longer significant.”
Quote in the paperSubstantial claim - Findingown data
Serum SHBG explained about 26% of the total variance in serum testosterone in the cohorts included in this study.
“In fact, in the cohorts included in this study SHBG explained about 26% of the total variance in serum T.”
Quote in the paperSubstantial claim - Premisecitation
Observational studies demonstrate that obesity is associated with low serum testosterone in men.
“Observational studies demonstrate that obesity is associated with low serum testosterone (T) [1]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] FC Wu, 2008, Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- Interpretationown data
The genetic risk scores can be used as largely un-confounded instruments to assess the causality of the inverse association between BMI and serum testosterone.
“This illustrates that these GRSs can be used as largely un-confounded instruments to assess the causality of the inverse association between BMI and serum T.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
- The authors state this as an assumption: Covariates are randomly distributed with respect to genotype.
- Study design and conductown data
Two separate independent genetic instruments (rs1558902 from FTO and a weighted risk score based on the remaining 96 SNPs) had similar point estimates of the causal effect of BMI on serum testosterone.
“These two independent genetic instruments had similar point estimates of the causal effect of BMI on serum T (S5 Table).”
Quote in the paperSubstantial claim - Premisecitation
A recent meta-analysis showed that body weight reductions from low-calorie diet and bariatric surgery are associated with significantly increased serum testosterone.
“This evidence of a causative effect of BMI on serum T is supported by a recent meta-analysis of the impact of body weight reduction on serum T, revealing that body weight reductions as a result of both low-calorie diet and bariatric surgery are associated with significantly increased serum T [37].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] G Corona, 2013, Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis, European journal of endocrinology / European Federation of Endocrine Societies source
Not checked in the free run.
- Interpretationown data
The study highlights the importance of considering obesity as a risk factor for low serum testosterone in men.
“Our study highlights the importance of considering obesity as a risk factor for low serum T in men with implications on the possible targeting of relevant health promotion strategies.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
- The authors state this as an assumption: A phenotypic trait cannot cause genetic variation, so Mendelian randomization analyses are free of reverse causation.
- The authors state this as an assumption: Covariates are randomly distributed with respect to genotype.
- Interpretationreasoning
For a body weight reduction altering BMI from 30 to 25 kg/m2, the effect would equal a 13-15% increase in serum testosterone.
“For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13–15% increase in serum T.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The genotypes are randomized.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- The authors state this as an assumption: The genotype is independent of confounders.
- Study design and conductown data
The study had approximately similar power to detect an association between BMI and testosterone using wGRSBMI (95%) compared with an equal sized effect in the other direction using wGRST (98%, n=7446).
“In theory, we had approximately similar power to detect an association between BMI and T using the wGRSBMI (95%) compared with an equal sized effect in the other direction using the wGRST (98%, n = 7446 subjects; S2 Fig).”
Quote in the paperNot a substantial claim - Interpretationown data
The magnitude of the causal effect of BMI on serum testosterone is similar to the observational association.
“The magnitude of this effect is similar to the observational association.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Low serum testosterone could contribute to the adverse health effects associated with obesity in men.
“low serum T could contribute to the adverse health effects associated with obesity in men.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
- The authors state this as an assumption: A phenotypic trait cannot cause genetic variation, so Mendelian randomization analyses are free of reverse causation.
- The authors state this as an assumption: Covariates are randomly distributed with respect to genotype.
- Interpretationreasoning
Population level interventions to reduce BMI are expected to increase serum testosterone in men.
“Population level interventions to reduce BMI are expected to increase serum testosterone in men.”
- Also stated in: § Discussion · hedged
“Population level interventions to reduce BMI are expected to increase serum T in men.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
- The authors state this as an assumption: A phenotypic trait cannot cause genetic variation, so Mendelian randomization analyses are free of reverse causation.
- The authors state this as an assumption: Covariates are randomly distributed with respect to genotype.
- Also stated in: § Discussion · hedged
- Interpretationown data
Genetically instrumented serum testosterone has no causal effect on BMI.
“No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349).”
- Also stated in: § Discussion · plain
“Conversely, our analyses provided no evidence for a causal role of serum T on BMI.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
- The authors state this as an assumption: A phenotypic trait cannot cause genetic variation, so Mendelian randomization analyses are free of reverse causation.
- The authors state this as an assumption: Covariates are randomly distributed with respect to genotype.
- Also stated in: § Discussion · plain
- Study design and conductown data
The present study was adequately powered to detect a causal association between BMI and testosterone if the strength of this association was equal to the observed association between serum BMI and testosterone.
“The present study was adequately powered to detect a causal association between BMI and T if the strength of this association was equal to the observed association between serum BMI and T.”
Quote in the paperNot a substantial claim - Interpretationown data
There is a causal effect of BMI on serum testosterone in men.
“The main finding in the present study is our results supporting a causal effect of BMI on serum T.”
- Also stated in: § Discussion · hedged
“In conclusion, our results suggest that there is a causal effect of BMI on serum T in men.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The genotypes are randomized.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- The authors state this as an assumption: The genotype is independent of confounders.
- Also stated in: § Discussion · hedged
- Premisecitation
The degree of body weight loss is a robust determinant of the increase in serum testosterone.
“Notably, this meta-analysis demonstrated that the degree of body weight loss is a robust determinant of the increase in serum T.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] G Corona, 2013, Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis, European journal of endocrinology / European Federation of Endocrine Societies source
Not checked in the free run.
- Interpretationown data
Higher BMI leads to lower serum testosterone in men.
“Our results suggest that there is a causal effect of BMI on serum testosterone in men.”
- Also stated in: § Discussion · plain
“Herein, we presented evidence that higher BMI leads to lower serum T.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
- The authors state this as an assumption: A phenotypic trait cannot cause genetic variation, so Mendelian randomization analyses are free of reverse causation.
- The authors state this as an assumption: Covariates are randomly distributed with respect to genotype.
- Also stated in: § Discussion · plain
- Interpretationown data
Increases in testosterone status are not likely to help with weight regulation in the general male population.
“These results suggest that although increases in T status are not likely to help with weight regulation in the general male population”
Quote in the paperSubstantial claim- The authors state this as an assumption: Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
- The authors state this as an assumption: A phenotypic trait cannot cause genetic variation, so Mendelian randomization analyses are free of reverse causation.
- The authors state this as an assumption: Covariates are randomly distributed with respect to genotype.
- Interpretationown data
The effect of BMI on serum testosterone is independent of SHBG.
“However, in the opposite analysis where serum T was the outcome and SHBG the covariate, wGRSBMI was significantly associated with serum T, supporting a SHBG-independent effect of BMI on serum T.”
Quote in the paperSubstantial claim - Interpretationreasoning
High BMI seems to repress serum testosterone mainly via central inhibitory effects on gonadotropin secretion.
“Thus high BMI seems to repress serum T mainly via central inhibitory effects on gonadotropin secretion [38, 41].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [38] P Dandona, 2011, Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- cites [41] F Saad, 2011, Onset of effects of testosterone treatment and time span until maximum effects are achieved, European journal of endocrinology / European Federation of Endocrine Societies source
Not checked in the free run.
- Interpretationown data
The close connection between serum testosterone and SHBG makes it difficult to discriminate between an effect directly on serum testosterone and an effect mediated via SHBG.
“This close connection between serum T and SHBG makes it difficult to discriminate between an effect directly on serum T and an effect mediated via SHBG.”
Quote in the paperSubstantial claim - Interpretationreasoning
We cannot discount a possible causative effect of severe testosterone deficiency on BMI.
“Consequently, we cannot discount a possible causative effect of severe T-deficiency on BMI.”
Quote in the paperSubstantial claim - Interpretationown data
The present study cannot determine the mechanism for the causal effect of obesity on serum testosterone.
“Although the present study provides compelling evidence that obesity reduces serum T levels, it cannot determine the mechanism for this causal effect which may occur at several levels of the hypothalamus-pituitary-gonadal axis.”
Quote in the paperSubstantial claim - Premisecitation
In morbidly obese men, LH levels and pulse amplitude are attenuated compared with normal-weight controls.
“It is well known that in morbidly obese men, LH levels and pulse amplitude are attenuated when compared with normal-weight controls [39, 40].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [39] VA Giagulli, 1994, Pathogenesis of the decreased androgen levels in obese men, The Journal of clinical endocrinology and metabolism
Not checked in the free run.
- cites [40] A Vermeulen, 1993, Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men, The Journal of clinical endocrinology and metabolism
Not checked in the free run.
- Interpretationown data
Male hypogonadism can be considered as one of the many adverse consequences of overweight and obesity.
“Our finding supports the notions that male hypogonadism can be considered as one of the many adverse consequences of overweight and obesity and that body weight loss and lifestyle interventions should be the first approach offered to obese men with low serum T [48].”
Quote in the paperSubstantial claim - Study design and conductown data
The different genetic risk scores used in the present study were not associated with age or smoking.
“For instance, although both BMI and T were associated with age and smoking, the different GRSs used in the present study were not associated with these two potential confounders.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The genotype is independent of confounders.
- Study design and conductcitation
There was a small overlap (less than 2%) between the cohorts used in the present study and the study by Locke et al that identified the BMI-associated SNPs.
“In the present study, there was a small overlap (less than 2%), between the cohorts used in the present study and the study by Locke et al that identified the BMI-associated SNPs[17].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] AE Locke, 2015, Genetic studies of body mass index yield new insights for obesity biology, Nature source
Not checked in the free run.
- Study design and conductown data
We did not detect any violations of the assumptions underlying MR as far as they could be tested.
“We did not detect any violations of the assumptions underlying MR as far as they could be tested.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The genotypes are randomized.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- The authors state this as an assumption: The genotype is independent of confounders.
- Study design and conductown data
Very similar results were obtained using an unweighted genetic risk score that avoids the potential bias from the use of internal weights.
“Firstly, very similar results were obtained using an unweighted genetic risk score that avoids the potential bias from the use of internal weights.”
Quote in the paperSubstantial claim - Study design and conductcitation
The use of two separate independent genetic instruments with similar point estimates of the causal effect of BMI on serum testosterone further reduced the risk of pleiotropy.
“Moreover, the use of two separate independent genetic instruments with similar point estimates of the causal effect of BMI on serum T further reduced the risk of pleiotropy [32, 33].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [32] G Davey Smith, 2011, Use of genetic markers and gene-diet interactions for interrogating population-level causal influences of diet on health, Genes Nutr source
Not checked in the free run.
- cites [33] PN Taylor, 2016, Paradoxical Relationship Between Body Mass Index and Thyroid Hormone Levels: A Study Using Mendelian Randomization, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- Study design and conductown data
Similar results were also obtained using a genetic risk score based solely on the SNP in the FTO gene.
“Secondly, similar results were also obtained using a genetic risk score based solely on the SNP in the FTO gene, which is a gene that has been found to be associated with BMI in numerous studies, where none of the cohorts used in the present study were included [34–36].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [34] TM Frayling, 2007, A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity, Science source
Not checked in the free run.
- cites [35] A Scuteri, 2007, Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits, PLoS genetics source
Not checked in the free run.
- cites [36] RJ Loos, 2008, Common variants near MC4R are associated with fat mass, weight and risk of obesity, Nat Genet source
Not checked in the free run.
- Interpretationown data
The participant data used in the present study were unrelated men with European ancestry, limiting the generalizability of the observed findings to other ethnic groups.
“The participant data used in the present study were unrelated men with European ancestry, limiting the generalizability of the observed findings to other ethnic groups.”
Quote in the paperNot a substantial claim - Study design and conductreasoning
There is a chance that the causal estimate calculated using the wGRSBMI could be biased due to overlap between cohorts.
“As a consequence, there is a chance that the causal estimate calculated using the wGRSBMI could be biased.”
Quote in the paperNot a substantial claim - Study design and conductown data
It is highly unlikely that the small cohort overlap has had a major impact on the results.
“It is, however, highly unlikely that this has had a major impact on the results for two reasons.”
Quote in the paperSubstantial claim - Study design and conductreasoning
A major influence from population stratification is unlikely in this study.
“However, this also means that a major influence from population stratification is unlikely.”
Quote in the paperSubstantial claim - Study design and conductcitation
Using 97 recently reported independent SNPs to index BMI minimized the risk of shared pleiotropy and linkage-disequilibrium-induced confounding pleiotropic effects.
“However, using as many as 97 recently reported independent SNPs to index BMI, we were able to minimize the risk of shared pleiotropy and linkage-disequilibrium-induced confounding pleiotropic effects [32, 33].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [32] G Davey Smith, 2011, Use of genetic markers and gene-diet interactions for interrogating population-level causal influences of diet on health, Genes Nutr source
Not checked in the free run.
- cites [33] PN Taylor, 2016, Paradoxical Relationship Between Body Mass Index and Thyroid Hormone Levels: A Study Using Mendelian Randomization, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- The authors state this as an assumption: The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
- May combine two claims. 23
- Classified as probably not a substantial claim. 10
May combine two claims.
Findingown dataBoth BMI and serum testosterone were associated with age and smoking (p<0.05).
“Although both BMI and serum T were associated with age and smoking (p<0.05)”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSub-analyses using two separate genetic risk scores based on SNPs within or outside the SHBG locus showed both were robustly associated with serum testosterone, but no evidence of significant associations between these testosterone genetic risk scores and BMI was observed.
“Although both these two separate T GRSs were robustly associated with serum T, no evidence of significant associations between these two separate T GRSs and BMI was observed (S7 Table).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataFor a body weight reduction altering BMI from 30 to 25 kg/m2, the effect would equal a 13% (wGRSBMI) to 15% (uwGRSBMI) increase in serum testosterone, while a corresponding observational effect would equal a 16% increase.
“Notably, for a body weight reduction altering the BMI from 30 (cut off for obesity) to 25 (cut off for overweight) kg/m2, the effect would equal a 13% (using IV ratio from wGRSBMI) to 15% (using IV ratio from uwGRSBMI) increase in serum T while a corresponding observational effect would equal a 16% increase in serum T (Fig 3).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe wGRSBMI and uwGRSBMI associations with testosterone did not vary by age or smoking (p>0.05).
“The wGRSBMI and uwGRSBMI associations with T did not vary by age or smoking (p > 0.05 for interaction terms in pooled analyses).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBoth wGRST and uwGRST were highly significantly associated with serum testosterone in the meta-analyzed combined data set (wGRST p=4.7*10−45, R2=2.5%; uwGRST p=3.9*10−38, R2=2.1%).
“Both wGRST and uwGRST were highly significantly associated with serum T in the meta-analyzed combined data set (wGRST p = 4.7*10−45, R2 = 2.5%; uwGRST p = 3.9*10−38, R2 = 2.1%; Fig 2B, S3 Table).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe wGRST and uwGRST associations with testosterone did not vary by age, smoking or BMI (p>0.05).
“The wGRST and uwGRST associations with T did not vary by age, smoking or BMI (p values > 0.05 for all interaction terms in pooled analyses).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBoth wGRSBMI and uwGRSBMI were highly significantly associated with ln-transformed BMI in all cohorts individually and when combined in meta-analysis (wGRSBMI p=4.2*10−35, R2=1.9%; uwGRSBMI p=5.0*10−27, R2=1.5%).
“Both wGRSBMI and uwGRSBMI were highly significantly associated with ln-transformed BMI in all cohorts individually and when combined in a meta-analytic approach (wGRSBMI p = 4.2*10−35, R2 = 1.9%; uwGRSBMI p = 5.0*10−27, R2 = 1.5%; Fig 2A, S1 Table).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe two BMI SNPs most robustly associated with BMI were also significantly associated with serum testosterone, but in the opposite direction (rs1558902 in FTO, p=4.0*10−2; rs6567160 in M4CR, p=3.0*10−3).
“Interestingly, the two BMI SNPs that were most robustly associated with BMI were also significantly associated with serum T, but in the opposite direction (rs1558902 in the FTO locus, p = 4.0*10−2 and rs6567160 in the M4CR locus, p = 3.0*10−3; S2 Table).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNeither wGRST nor uwGRST was associated with BMI.
“Neither the wGRST nor the uwGRST was associated with BMI (Fig 2D, S3 Table).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe two SNPs most robustly associated with BMI in the present study are also significantly associated with serum testosterone but in the opposite direction.
“Notably, the two SNPs most robustly associated with BMI in the present study are also significantly associated with serum T but in the opposite direction.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBoth wGRST and uwGRST were significantly associated with SHBG in the present study.
“In line with this, both wGRST and uwGRST were significantly associated with SHBG in the present study.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBoth separate T GRSs (within and outside the SHBG locus) were robustly associated with serum testosterone, but no evidence of significant associations between these T GRSs and BMI was observed.
“Although both these two separate T GRSs were robustly associated with serum T, no evidence of significant associations between these two separate T GRSs and BMI was observed.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenTwo independent instrumental variables were used for each phenotype to assess pleiotropy.
“Two independent instrumental variables were used for each phenotype to assess pleiotropy.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationMost randomized, placebo-controlled trials have indicated that testosterone treatment increases lean mass and reduces fat mass in men with low serum testosterone.
“Most randomized, placebo-controlled trials have indicated that T treatment increases lean mass and reduces fat mass in men with low serum T [2–7]”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [2] MR Blackman, 2002, Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial, Jama source
Not checked in the free run.
- cites [3] AM Kenny, 2001, Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
- cites [4] ST Page, 2005, Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- cites [5] PJ Snyder, 1999, Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age, The Journal of clinical endocrinology and metabolism
Not checked in the free run.
- cites [6] U Srinivas-Shankar, 2010, Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- cites [7] F Saad, 2012, Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review, Curr Diabetes Rev source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe largest genome wide association study on serum testosterone identified three independent genetic variants associated with serum testosterone in men.
“while the largest GWAS on serum T identified three independent genetic variants associated with serum T in men [17, 18].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] C Ohlsson, 2011, Genetic determinants of serum testosterone concentrations in men, PLoS genetics source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe overall effect of testosterone treatment on body weight and BMI in men with different testosterone status is inconsistent.
“but the overall effect on body weight and BMI in men with different T-status is inconsistent.”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [2] MR Blackman, 2002, Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial, Jama source
Not checked in the free run.
- cites [3] AM Kenny, 2001, Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, J Gerontol A Biol Sci Med Sci source
Not checked in the free run.
- cites [4] ST Page, 2005, Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- cites [5] PJ Snyder, 1999, Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age, The Journal of clinical endocrinology and metabolism
Not checked in the free run.
- cites [6] U Srinivas-Shankar, 2010, Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
- cites [7] F Saad, 2012, Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review, Curr Diabetes Rev source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe most recent and largest genome wide association study on BMI identified 97 independent genetic variants associated with BMI.
“The most recent and largest genome wide association study (GWAS) on BMI identified 97 independent genetic variants associated with BMI”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] AE Locke, 2015, Genetic studies of body mass index yield new insights for obesity biology, Nature source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationSerum testosterone was measured using validated gas chromatography/mass spectroscopy in GOOD and MrOS Sweden.
“GOOD and MrOS Sweden used a validated gas chromatography/mass spectroscopy (intra-assay CV, 2.9%; inter-assay CV, 3.4%) to measure serum T [20].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] L Vandenput, 2007, Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men, J Bone Miner Res source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenLinearity was assessed by adding a quadratic term to the regression analyses.
“Linearity was assessed by adding a quadratic term to the regression analyses.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningThe associations between genotype and known confounders (age and smoking) were examined as a key assumption in Mendelian randomization analyses.
“the associations between genotype and known confounders (age and smoking) were examined as this is a key assumption in MR analyses.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataThe F-statistics for wGRST and uwGRST were 188 and 156, respectively.
“The F-statistics were 188 and 156 for wGRST and uwGRST, respectively (S3 Table).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationCross-sectional data from EMAS showed that BMI was the strongest determinant of serum testosterone and obese men (BMI > 30 kg/m2) had as much as 1.47 ng/ml lower serum testosterone compared with normal weight subjects (BMI < 25 kg/m2).
“Cross-sectional data from the large European Male Aging Study (EMAS) revealed that BMI was the strongest determinant of serum T and obese men (BMI > 30 kg/m2) had as much as 1.47 ng/ml lower serum T compared with normal weight subjects (BMI < 25 kg/m2; [1]).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] FC Wu, 2008, Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
May combine two claims.
Study design and conductown dataThe F-statistics for wGRSBMI and uwGRSBMI were 147 and 111, respectively.
“The F-statistics, reflecting the strength of the instruments, were 147 and 111 for wGRSBMI and uwGRSBMI, respectively (S1 Table).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationObese subjects often have reduced gonadotropin concentrations, indicating that the primary effect is mediated at the hypothalamus-pituitary level rather than at the testicular level.
“Obese subjects often have reduced gonadotropin concentrations indicating that the primary effect is mediated at the hypothalamus-pituitary level rather than at the testicular level [38].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [38] P Dandona, 2011, Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity, The Journal of clinical endocrinology and metabolism source
Not checked in the free run.
May combine two claims.
PremisecitationMean percent body weight loss at endpoint was 10% in low-calorie diet studies and 32% in bariatric surgery studies, with corresponding increases in serum testosterone of 0.83 ng/ml and 2.54 ng/ml, respectively.
“The mean percent body weight loss at endpoint was 10% in low-calorie diet studies and 32% in bariatric surgery studies and the corresponding increases in serum T levels were 0.83 ng/ml and 2.54 ng/ml, respectively.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] G Corona, 2013, Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis, European journal of endocrinology / European Federation of Endocrine Societies source
Not checked in the free run.
May combine two claims.
PremisecitationBody weight reduction increases not only serum testosterone but also gonadotropins FSH and LH, suggesting that body weight loss reverses obesity-associated hypogonadotropic hypogonadism.
“Not only serum T but also the gonadotropins FSH and LH were increased by body weight reduction, suggesting that body weight loss reverses obesity-associated hypogonadotropic hypogonadism [37].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] G Corona, 2013, Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis, European journal of endocrinology / European Federation of Endocrine Societies source
Not checked in the free run.
May combine two claims.
PremisecitationThe MR approach enables the approximation of life-long differences in average concentrations, but genetic markers do not examine the influences arising from the extremes of non-linear distributions.
“While the MR approach enables the approximation of life-long differences in average concentrations, genetic markers do not examine the influences arising from the extremes of non-linear distributions [28, 50].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [28] KS Vimaleswaran, 2013, Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts, PLoS medicine source
Not checked in the free run.
- cites [50] J Zheng, 2011, A comparison of approaches to account for uncertainty in analysis of imputed genotypes, Genet Epidemiol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe underlying loci of these two SNPs, FTO and MC4R, are well established obesity-related loci.
“The underlying loci of these two SNPs, FTO and MC4R, are well established obesity-related loci [35, 36, 45].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [35] A Scuteri, 2007, Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits, PLoS genetics source
Not checked in the free run.
- cites [36] RJ Loos, 2008, Common variants near MC4R are associated with fat mass, weight and risk of obesity, Nat Genet source
Not checked in the free run.
- cites [45] S Peng, 2011, FTO gene polymorphisms and obesity risk: a meta-analysis, BMC Med source
Not checked in the free run.
May combine two claims.
PremisecitationTwo of the three SNPs constituting the genetic risk score for BMI reside in the SHBG locus and have previously been reported to associate with SHBG.
“Two of the three SNPs constituting the genetic risk score for BMI reside in the SHBG locus and have previously been reported to associate with SHBG (18).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] C Ohlsson, 2011, Genetic determinants of serum testosterone concentrations in men, PLoS genetics source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe FTO locus has previously been reported to be associated with affected androgen levels, polycystic ovary syndrome susceptibility and age at menarche in females.
“The FTO locus has previously been reported to be associated with affected androgen levels, polycystic ovary syndrome susceptibility and age at menarche in females while its impact on serum T and T-related diseases in men is unknown and warrants further investigations [46, 47].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [46] CE Elks, 2010, Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies, Nat Genet source
Not checked in the free run.
- cites [47] K Song do, 2014, FTO Gene Variants Are Associated with PCOS Susceptibility and Hyperandrogenemia in Young Korean Women, Diabetes Metab J source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenParticipants were included at random and consecutively from the general population, so the potential for selection bias is minimal.
“Also, as we included participants at random and consecutively from the general population, the potential for selection bias is minimal.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe validity of our findings was strengthened by very similar results for weighted and unweighted genetic risk scores and when combined estimates were calculated using pooling and a meta-analytic approach.
“The validity of our findings was strengthened by the fact that very similar results were obtained for both weighted and un-weighted genetic risk scores and when combined estimates were calculated using pooling and a meta-analytic approach.”
Quote in the paperSubstantial claim
The authors state this as an assumption.
Genetic variants are randomly distributed with respect to confounding factors because they are fixed at conception.
“Since genes can be thought of as randomized and fixed at conception, confounding factors will be equally distributed among different genotypes.”
The authors state this as an assumption.
A phenotypic trait cannot cause genetic variation, so Mendelian randomization analyses are free of reverse causation.
“Furthermore, it will be free of reverse causation since a phenotypic trait cannot cause genetic variation.”
The authors state this as an assumption.
Covariates are randomly distributed with respect to genotype.
“although covariates are expected to be randomly distributed with respect to genotype, the associations between genotype and known confounders (age and smoking) were examined as this is a key assumption in MR analyses.”
The authors state this as an assumption.
The genotypes are randomized.
“Three key assumptions underlie the MR randomization approach: the genotypes are randomized; the genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome; and the genotype is independent of confounders [27, 30, 31].”
The authors state this as an assumption.
The genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome.
“Three key assumptions underlie the MR randomization approach: the genotypes are randomized; the genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome; and the genotype is independent of confounders [27, 30, 31].”
The authors state this as an assumption.
The genotype is independent of confounders.
“Three key assumptions underlie the MR randomization approach: the genotypes are randomized; the genetic variants considered as instruments affect the outcome only by modifying the biomarker—that is, these variants have no pleiotropic effects on the outcome; and the genotype is independent of confounders [27, 30, 31].”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A bidirectional Mendelian randomization study suggested that the effect of an elevated BMI on low testosterone is more important than the effect of low testosterone on an increased BMI, but requires confirmation in independent samples.
“While a bidirectional Mendelian randomization study suggested that the effect of an elevated BMI on low testosterone is more important than the effect of low testosterone on an increased BMI, such studies require confirmation in independent samples. 63”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [63]
BMI has a causal effect on testosterone, whereas testosterone does not impact BMI.
“Consistent with the foregoing discussion, the authors concluded that BMI has a causal effect on testosterone, whereas testosterone does not impact BMI.”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [59]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
BMI genetic risk score is described as containing three SNPs instead of 97
MinorThe methods state that the BMI genetic risk score is based on 97 SNPs, but the discussion describes it as containing three. The three-SNP score is identified elsewhere as the testosterone score.
“Two of the three SNPs constituting the genetic risk score for BMI reside in the SHBG locus and have previously been reported to associate with SHBG (18).”
“The 97 BMI-associated SNPs identified in a recent large-scale GWAS on BMI were used to construct a weighted genetic risk score, wGRSBMI”
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Mannelijk hypogonadisme, een update
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- Authors
- Eriksson, J., Haring, R., Grarup, N., Vandenput, L., Wallaschofski, H., Lorentzen, E., Hansen, T., Mellström, D., Pedersen, O., Nauck, M., Lorentzon, M., Nystrup Husemoen, L. L., Völzke, H., Karlsson, M., Baumeister, S. E., Linneberg, A., & Ohlsson, C.
- Affiliations
- University of Gothenburg (SE)
- Universitätsmedizin Greifswald (DE)
- University of Copenhagen (DK)
- Lund University (SE)
- Corresponding author
- Ohlsson, Claes
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-04-27
- Volume
- 12
- Issue
- 4
- Pages
- e0176277
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5407807
- OpenAlex
- W2609007932
- Semantic Scholar
- baed90fa3c006d6d7e42dbea4c5f18ef579c7240
- Cited by
- 101
- References
- 56
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 15 · 2021: 17 · 2020: 15 · 2019: 10 · 2018: 13
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- Research Bank (Australian Catholic University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Vetenskapsrådet (2011-2535)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- obesity, serum testosterone, body mass index, men, causal relationship, weight loss, androgen deficiency, metabolic syndrome
- MeSH terms
- Adolescent, Adult, Aged, Humans, Male, Obesity, Phenotype, Testosterone, Body Mass Index, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Young Adult, Mendelian Randomization Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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