Cited by 1,496Genetic Associations and EpidemiologyAdvanced Causal Inference TechniquesGenetics and Physical Performance

The DOI matches its Crossref record; 120 of the 120 references it cites were found in a registry or an index.

Evaluating the potential role of pleiotropy in Mendelian randomization studies

Open access

Hemani, Gibran, Bowden, Jack, Davey Smith, George·2018·Human Molecular Genetics

DOI 10.1093/hmg/ddy163PMC PMC6061876

Open this paper in CoChat — free account Open PDF

Abstract

Pleiotropy, the phenomenon of a single genetic variant influencing multiple traits, is likely widespread in the human genome. If pleiotropy arises because the single nucleotide polymorphism (SNP) influences one trait, which in turn influences another ('vertical pleiotropy'), then Mendelian randomization (MR) can be used to estimate the causal influence between the traits. Of prime focus among the many limitations to MR is the unprovable assumption that apparent pleiotropic associations are mediated by the exposure (i.e. reflect vertical pleiotropy), and do not arise due to SNPs influencing the two traits through independent pathways ('horizontal pleiotropy'). The burgeoning treasure trove of genetic associations yielded through genome wide association studies makes for a tantalizing prospect of phenome-wide causal inference. Recent years have seen substantial attention devoted to the problem of horizontal pleiotropy, and in this review we outline how newly developed methods can be used together to improve the reliability of MR.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1093/hmg/ddy163

Cites

120 of 120 references verified0 citation errors · 0 not checkable

Statistics

Figure 1. (A) The same SNP can associate with multiple traits due to vertical pleiotropy, horizontal pleiotropy and linkage disequilibrium with distinct causal variants depending on the analytical context. To estimate the causal influence of gene expression level (Gene) 1 on Trait 1, SNP 1 is a valid instrument that acts in a vertical pleiotropic manner. But SNP 1 has a horizontal pleiotropic effect when using it to estimate the causal influence of Gene 1 on Trait 2. If SNP 1 was used to instrument Gene 1 to test its effect on Trait 3, it would exhibit a pleiotropic association through linkage disequilibrium with SNP 2. (B) A directed acyclic graph (DAG) in which four SNPs instrument an exposure. The fourth SNP has a horizontal pleiotropic effect of magnitude α. The impact of the horizontal pleiotropic effect is shown in the scatter plot in (C), where the grey slope represents the true causal effect obtained from the three valid instruments, and the red slope represents the IVW estimate when all SNPs are used as instruments.CC BY · PubMed Central

Appendix figure 1. (A) Unobserved confounding (U) makes it impossible to be fully confident that an association between risk factor X and outcome Y represents a measure of causal effect of X on Y. (B) In a perfect RCT, randomization to treatment (T) removes the possibility of confounding, enabling the causal effect of T on Y to be estimated. (C) MR uses genetic variants (G) that explain some variation in the exposure X to estimate the causal effect of X on Y. G must satisfy the instrumental variable assumptions, encoded by the solid arrows (and the strict absence of the dotted arrows) in (C). (D) Instrumental variable methods can also be used in clinical trials when randomization is imperfect because some patients do not receive the treatment they were originally assigned. This is referred to as `non-compliance’. An MR analysis is conceptually and mathematically equivalent to the analysis of RCT data in the presence of non-compliance, where the SNP (G) and exposure (X) proxy for randomization (R) and treatment (T), respectively.CC BY · PubMed Central

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · cited 1×
“Independence is often ensured using LDbased clumping and pruning (45).”
Method
Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression
Bowden, J., Davey Smith, G., & Burgess, S. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv080 · Cited by 9,816 · cited 3×
“Here, it is assumed that on an average the random effects have zero mean and are uncorrelated with the SNP-exposure effect (55) (Appendix 1).”
BackgroundMethodSelf-citation
Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator
Bowden, J., Davey Smith, G., Haycock, P. C., & Burgess, S. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21965 · Cited by 8,922 · cited 2×
“This can be extended to a more efficient weighted analysis, which then requires that the set of instruments accounting for 50% or more of the total weight is valid (64).”
BackgroundSelf-citation
Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases
Verbanck, M., Chen, C.-Y., Neale, B., & Do, R. (2018) · Nature Genetics · doi:10.1038/s41588-018-0099-7 · Cited by 8,591 · cited 3×
“based heterogeneity and outlier test is proposed within MR-PRESSO (61), which performs similarly to modified second-order”
BackgroundMethod
The MR-Base platform supports systematic causal inference across the human phenome
Hemani, G., Zheng, J., Elsworth, B., Wade, K. H., Haberland, V., Baird, D., Laurin, C., Burgess, S., Bowden, J., Langdon, R., et al. (2018) · eLife · doi:10.7554/elife.34408 · Cited by 7,959 · cited 8×
“It is also common to see leaveone-out analyses where the causal effect is re-estimated but sequentially omitting a particular instrument each time, to evaluate if any one variant is driving the analysis (8).”
BackgroundMethodResultInfluentialSelf-citation
‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?*
Davey Smith, G., & Ebrahim, S. (2003) · International Journal of Epidemiology · doi:10.1093/ije/dyg070 · Cited by 5,882 · cited 3×
“In these cases, extending the analogy to RCTs, each instrumenting SNP is considered an independent experiment (in the sense that they independently modify the exposure), and as such the results from each experiment can be meta-analysed to give an overall estimate (7,46,47).”
Method
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
Mendelian randomization: genetic anchors for causal inference in epidemiological studies
Davey Smith, G., & Hemani, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu328 · Cited by 4,677 · cited 5×
“In these cases, extending the analogy to RCTs, each instrumenting SNP is considered an independent experiment (in the sense that they independently modify the exposure), and as such the results from each experiment can be meta-analysed to give an overall estimate (7,46,47).”
MethodInfluentialSelf-citation
Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics
Giambartolomei, C., Vukcevic, D., Schadt, E. E., Franke, L., Hingorani, A. D., Wallace, C., & Plagnol, V. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004383 · Cited by 4,261 · cited 4×
“The R/coloc (25) package uses summary data for the SNPs in a region and estimates the posterior probability of shared genetic factors by evaluating the similarity of effect size patterns across the region.”
BackgroundMethodInfluential
Identification and estimation of local average treatment effects
Imbens, G. W., & Angrist, J. D. (1994) · Econometrica · doi:10.2307/2951620 · Cited by 4,101

Show all 113 references

Research works printed but not linked: 1

Purcell, 2009, International Schizophrenia Consortium, Nature, 460, 748

Sorted by citations

Items 801–900 of 1,001

Mendelian Randomization Identifies CD25+ CD4+ Tregs and Plasma Proteins in Androgenetic Alopecia Pathogenesis
Du, Y., Du, Y., Yu, Y., Huang, Y., Fan, W., & Wang, L. (2025) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s541690 · Cited by 3
TERT activator compound alleviates cigarette smoke-induced cognitive deficits by modulating hippocampal inflammation and neurogenesis: A comprehensive study integrating Mendelian randomization
Zheng, Z., Chen, C., Zhu, S., Zhu, X., Tu, H., Ding, X., Xia, T., & Gu, X. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115543 · Cited by 3
Pre-existing pulmonary function abnormality exacerbates the impact of occupational dust exposure on incident hypertension: Evidence from a large occupational cohort
Xu, Z., Xu, X. P., Shao, L., Xia, B., Zhou, S., Wang, S., Guo, Y., Lin, L., Zhong, H., Liu, L., et al. (2025) · Hygiene and Environmental Health Advances · doi:10.1016/j.heha.2025.100157 · Cited by 3
Causal Relationships Between Pregnancy, Menstrual History, and Endometrial Cancer With Mediating Effects of Metabolism‐Related Traits
Zhou, M., Dai, S., Zhu, T., & Hong, S. (2025) · Human Mutation · doi:10.1155/humu/3401957 · Cited by 3
The Association Between Irritable Bowel Syndrome and Generalized Anxiety Disorder and Influencing Factors: A Mediation Mendelian Randomization Study
Yang, W., Wang, Y., Wang, S., Zhai, H., Che, J., Wang, X., Yang, Y., & Jia, Z. (2026) · Food Science & Nutrition · doi:10.1002/fsn3.71525 · Cited by 3
“Leave- one-out was also executed to evaluate whether the IVW estimate was overly influenced by individual SNPs (Hemani, Bowden, and Davey Smith 2018).”
Using genetics to detangle the relationships between red cell distribution width and cardiovascular diseases: a unique role for body mass index
Thayer, T. E., Huang, S., Farber‐Eger, E. H., Beckman, J. A., Brittain, E. L., Mosley, J. D., & Wells, Q. S. (2021) · Open Heart · doi:10.1136/openhrt-2021-001713 · Cited by 3
Mendelian randomization study reveals the effect of idiopathic pulmonary fibrosis on the risk of erectile dysfunction
Zhang, K., Zhou, J., Li, A., & Chen, M. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1162153 · Cited by 3
Modifiable factors for benign salivary gland neoplasms: A Mendelian randomization study
Gao, Y., Chen, H., Liu, Y., Zhang, X., Qiu, Y., & Huang, D. (2024) · Oral Diseases · doi:10.1111/odi.14682 · Cited by 3
Bias and mean squared error in Mendelian randomization with invalid instrumental variables
Deng, L., Fu, S., & Yu, K. F. (2023) · Genetic Epidemiology · doi:10.1002/gepi.22541 · Cited by 3
Mendelian randomization analysis reveals causal associations of inflammatory bowel disease with Spondylarthritis
Wang, M., & He, X. (2024) · Gene · doi:10.1016/j.gene.2024.148170 · Cited by 3
Impact of habitual intake of glucosamine, fresh fruit, and tea on the risk of urolithiasis: A two-sample Mendelian randomization study
Pan, Y., Su, J., Qian, S., & Xu, G. (2024) · Medicine · doi:10.1097/md.0000000000037254 · Cited by 4
“[32] All p-values were expressed in a 2-tailed manner with a significance level affixed at P .05.”
Method
Association between body mass index and electrocardiogram indices: A Mendelian randomization study
Yang, J., Chen, Y., & Li, W. (2024) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2024.03.007 · Cited by 3
A mediation analysis framework based on variance component to remove genetic confounding effect
Dong, Z., Zhao, H., & DeWan, A. T. (2024) · Journal of Human Genetics · doi:10.1038/s10038-024-01232-x · Cited by 4
“While vertical pleiotropy is de ﬁ ned that a genetic factor directly in ﬂ uences the ﬁ rst phenotype, and indirectly in ﬂ uences the second phenotype through the ﬁ rst phenotype (the mediator) [3].”
Metabolic Traits and Risk of Ischemic Stroke in Japanese and European Populations: A Two-Sample Mendelian Randomization Study
Zhang, J., Lu, H., Cao, M., Zhang, J., Liu, D., Meng, X., Zheng, D., Wu, L., Liu, X., & Wang, Y. (2024) · Metabolites · doi:10.3390/metabo14050255 · Cited by 3
“Additionally, the results of this study also need to be further verified by data from other East Asian populations.”
Result
Genetically predicted major depression causally increases the risk of temporomandibular joint disorders
Wu, S., Chen, Z., Zhao, Y., He, Q., Yin, Z., Yao, H., Liu, H., & Yan, L. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1395219 · Cited by 3
Gut Microbiota, Human Blood Metabolites, and Esophageal Cancer: A Mendelian Randomization Study
Xiuzhi, L. I., Xu, B., Yang, H., & Zhu, Z. (2024) · Genes · doi:10.3390/genes15060729 · Cited by 4
“An assessment of the heterogeneity between SNPs was carried out using Cochran’s Q statistics [27].”
Method
Allergic diseases and Meniere's disease: a bidirectional Mendelian randomization
Qin, H., Huang, M., Liang, W., Wu, G., Tan, M., Zhang, J., & Chen, W. (2024) · Brazilian Journal of Otorhinolaryngology · doi:10.1016/j.bjorl.2024.101472 · Cited by 3
Exploring the genetic causal relationship between physical activity and migraine in European population based on Mendelian randomization analysis
Wang, J., & Yang, G. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1434433 · Cited by 3
“In this study, we conducted a bidirectional two-sample MR study using the TwoSample-MR 3.2R package developed by researchers on the MR-base platform (27).”
Method
Research on the causal relationship between fine particulate matter and type 2 diabetes mellitus: A two-sample multivariable mendelian randomization study
Shou, X., Yao, Z., Wang, Y., Chai, Y., Huang, Y., Chen, R., Gu, W., & Liu, Q. (2024) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2024.08.023 · Cited by 3
Association of depression with gastroesophageal reflux disease, and the mediating role of risk factors: a Mendelian randomization study
Duan, H., Tao, L., Wu, K., Li, Q., Zhou, X., Dong, P., Sun, X., Lin, L., Ma, X., Zhao, R., et al. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1425730 · Cited by 4
“We cannot completely rule out violations of the independence assumption because we do not know the biological role of the genetic tools, and exclusionary restrictions, especially with respect to pleiotropy (84).”
Genetic Variation in Targets of Antidiabetic Drugs and Amyotrophic Lateral Sclerosis Risk
Wan, M., Zhang, L., Huo, J., Fu, Y., Huang, T., & Fan, D. (2024) · Biomedicines · doi:10.3390/biomedicines12122733 · Cited by 3
“The Wald ratio method was used when there was only one SNP [30].”
Systematic functional characterization of non-coding regulatory SNPs associated with central obesity
Dong, S.-S., Duan, Y.-Y., Zhu, R., Jia, Y., Chen, J., Huang, X., Tang, S., Yu, K., Shi, W., Chen, X., et al. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2024.11.005 · Cited by 3
Causal effects of blood cells on breast cancer: Evidence from bidirectional Mendelian randomization combined with meta-analysis
Liu, Q., Jia, W., Zhang, Y., Lu, J. L., Luo, Q., Yang, L., & Wan, D. (2025) · Medicine · doi:10.1097/md.0000000000041545 · Cited by 3
Causal relationship between rosacea and psychiatric disorders: a bidirectional two-sample Mendelian randomization study
Li, Y., Hu, T., Jiang, L., & Ge, L. (2025) · Archives of Dermatological Research · doi:10.1007/s00403-025-04142-w · Cited by 3
The Relationship Between Serum Uric Acid and Gynecologic Cancer Risk: A Mendelian Randomization Study
Cai, L., & Yang, C. K. (2025) · International Journal of Women s Health · doi:10.2147/ijwh.s493564 · Cited by 2
Mendelian Randomization Studies: A Metric for Quality Evaluation
Rosas-Chavez, F., & Merriman, T. R. (2025) · Gout Urate and Crystal Deposition Disease · doi:10.3390/gucdd3020008 · Cited by 4
“Bidirectional studies, which test both the effect of the exposure on the outcome and the effect of the outcome on the exposure, were assigned 1 point because positive associations in both directions may indicate the presence of confounding factors [21].”
Bidirectional causal relationship between obesity and osteoarthritis: Insights from a two-sample Mendelian randomization study
Kamps, A., Runhaar, J., Trajanoska, K., Thompson, W., Zhang, W., Sedaghati-khayat, B., van Meurs, J. B. J., & Bierma‐Zeinstra, S. (2025) · Osteoarthritis and Cartilage Open · doi:10.1016/j.ocarto.2025.100636 · Cited by 3
“The IVW method does not tolerate heterogeneity in the genetic variants, risking biased estimates despite the use of a random effects model [23].”
Repurposing Acebutolol for Osteoporosis Treatment: Insights From Multi‐Omics and Multi‐Modal Data Analysis
Liu, D., Shen, H., Greenbaum, J., Yi, Q., Liang, S., Zhang, Y., Liu, J., Qiu, C., Zhao, L., Tian, Q., et al. (2025) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3738 · Cited by 3
“25”
Search for common genetic variants to allow reliable Mendelian randomization investigations into ketone metabolism
Jiesisibieke, Z. L., Cronjé, H. T., Schooling, C. M., & Burgess, S. (2025) · European Journal of Epidemiology · doi:10.1007/s10654-025-01246-5 · Cited by 4
“Note: Estimates represent per allele associations of variants with each ketone body in standard deviation units pathways to the outcome (i.e. horizontal pleiotropy) [41].”
The role of mitochondria-related proteins in inflammation and autoimmune diseases: a causal analysis using Mendelian randomization and colocalization
Hong, Y. (2025) · Health Information Science and Systems · doi:10.1007/s13755-025-00358-2 · Cited by 5
“Previous studies have suggested that significant MR results may sometimes arise from loci where SNPs are in close linkage disequilibrium, with the SNP-exposure and SNP-outcome associations potentially stemming from distinct causal SNPs [41].”
Causal Relationship between Chronic Gastritis and Sleep Apnea Syndrome: A Bidirectional and Two-step Mendelian Randomization Study
Zhao, Z., Zhu, Y., You, C., Wang, Y., Zhuang, T., & Yang, Y. (2025) · Life Conflux · doi:10.71321/zrtsfk74 · Cited by 3
“Sensitivity analysis After the preliminary screening, we evaluated the heterogeneity of the Cochran’s Q test of IVW and MR-Egger methods for the significant results, and when p 0.05, significant heterogeneity was considered to be present [26].”
Influential
Shared genomic architectures of COVID-19 and antisocial behavior
Adams, C. D., Tielbeek, J. J., & Boutwell, B. B. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01948-4 · Cited by 3
“But with all the traits in our matrix, the prevailing direction of effect could be the opposite and/or some level of bi-directional causation may exist [16, 21 – 23].”
Serum 25-hydroxyvitamin D levels and the risk of non-alcoholic fatty liver
Sheng, Q., Shi, H., Liu, S., Zhuang, L., Zhao, Z., & Xin, Y. (2022) · Saudi Journal of Gastroenterology · doi:10.4103/sjg.sjg_297_22 · Cited by 3
Estimating the causal effects of genetically predicted plasma proteome on heart failure
Yang, J., Yan, B., Zhang, H., Lu, Q., Yang, L., Liu, P., & Bai, L. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.978918 · Cited by 3
“Furthermore, we removed horizontal pleiotropic outliers using the MR-PRESSO method and evaluated the presence of horizontal pleiotropy using the MR-Egger intercept test (33), Cochran Q test (34), and leave-one-out analyses (35).”
Method
Trans-ethnic Mendelian randomization study of systemic lupus erythematosus and common female hormone-dependent malignancies
Zhu, T., Ding, Y., Xu, X., Zhang, L., Zhang, X., Cui, Y., & Liu, L. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002555 · Cited by 4
“The procedures were similar to those described earlier, including IVW analysis and a panel of sensitivity analyses.”
Method
Evaluating the causality between skin tanning, radiated disorders, and basal cell carcinoma: a multivariable Mendelian randomization analysis
Chen, C., Wan, B., Lu, W., & Lu, J. (2023) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-27420-4 · Cited by 3
“05) was not observed, a fixed-effects model was employed; otherwise, a random-effects model was applied (Hemani et al. 2018).”
Method
Tea consumption and risk of lung diseases: a two‑sample Mendelian randomization study
Chen, L., Deng, Y., Wang, T., Lin, X., Zheng, L., Chen, X., & Chen, T. (2023) · BMC Pulmonary Medicine · doi:10.1186/s12890-023-02762-4 · Cited by 3
Causal associations between liver enzymes and diabetic microvascular complications: A univariable and multivariable Mendelian randomization
Li, Y., & Zhang, Q. (2024) · PLoS ONE · doi:10.1371/journal.pone.0296894 · Cited by 3
Resting heart rate and risk of dementia: a Mendelian randomization study in the international genomics of Alzheimer’s Project and UK Biobank
Chen, X., Zheng, Y., Wang, J., Yue, B., Zhang, X., Nakai, K., & Yan, L. L. (2024) · PeerJ · doi:10.7717/peerj.17073 · Cited by 3
Association between non-scarring alopecia and hypothyroidism: a bidirectional two-sample Mendelian randomization study
Yang, J., Zhu, Z., Zhang, C., Guo, Y., Wang, G., & Fu, M. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1356832 · Cited by 3
“We also utilized the RAPS method to address issues concerning the bias of weak IVs and to improve the robustness of causal estimates.”
MethodInfluential
Genetic predisposition to childhood obesity does not influence the risk of developing skin cancer in adulthood
Keatley, J., Law, M. H., Seviiri, M., Olsen, C. M., Pandeya, N., Ong, J., MacGregor, S., Whiteman, D. C., & Dusingize, J. C. (2024) · Scientific Reports · doi:10.1038/s41598-024-58418-8 · Cited by 3
“All MR analyses carry the risk of pleiotropy, whereby a genetic variant is involved in pathways that influence both the exposure and the outcome 12 .”
Background
Evaluation of bi-directional causal association between periodontitis and benign prostatic hyperplasia: epidemiological studies and two-sample mendelian randomization analysis
Wei, H., Tian, G., Xu, S., Du, Y., Li, M., Wang, Y., Deng, J., & Quan, C. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1326434 · Cited by 3
Genetically determined type 1 diabetes mellitus and risk of osteoporosis
Cheng, T., Hou, J.-L., Han, Z., Geng, X.-L., Zhang, Y., Fan, K., Liu, L., Zhang, H., Huo, Y.-H., Li, X., et al. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112434 · Cited by 3
“Violations of the second and third assumptions occur if horizontal pleiotropy exists (a genetic variant affects the outcome variable through pathways other than or in addition to the exposure variable (Hemani et al., 2018)).”
Background
No genetic causal association between periodontitis and ankylosing spondylitis: a bidirectional two-sample mendelian randomization analysis
Han, C., Wu, D., Yu, F., Wang, Q., Yang, Y., Li, Y., Qin, R., Chen, Y., Xu, L., & He, D. (2024) · BMC Medical Genomics · doi:10.1186/s12920-024-01845-3 · Cited by 3
“…to investigate the causality of PD with AS. MR studies use genetic variation as an IV, and a valid IV must satisfy the following three assumptions [17]: (1) it must be strongly associated with exposure (“relevance”); (2) it must be independent of confounding factors for observational associations…”
Background
Evaluation of bi-directional causal association between obstructive sleep apnoea syndrome and diabetic microangiopathy: a Mendelian randomization study
Liu, Q., Chang, X., Lian, R., Chen, Q., Wang, J., & Fu, S. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1340602 · Cited by 3
Effects of antidiabetic agents on platelet characteristics with implications in Alzheimer's disease: Mendelian randomization and colocalization study
Xie, Z., Liu, Y., Huang, M., Zhong, S., & Lai, W. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e30909 · Cited by 3
“Moreover, Cochran ’ s Q test was performed to test heterogeneity within IVs, and genetic pleiotropy was also diagnosed in this study [25].”
Method
Causal relationship between neuroticism and frailty: A bidirectional Mendelian randomization study
Chen, Q., Gan, D., Zhang, Y., Yan, R., Li, B., Tang, W., Han, S., & Gao, Y. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.05.105 · Cited by 3
Exploring the causal association between serum metabolites and erectile dysfunction: a bidirectional Mendelian randomisation study
Xu, R., Liu, S., Li, L., Bu, Y., Bai, P., Luo, G., & Wang, X. (2024) · International Journal of Impotence Research · doi:10.1038/s41443-024-00926-2 · Cited by 4
RETRACTED: Serum lipids may causally affect the occurrence of alopecia areata: A Mendelian randomization study
Chen, J., Dai, X., Lin, S., Liu, J., Li, Q., Xie, Z., He, Z., & Ye, X. (2024) · Skin Research and Technology · doi:10.1111/srt.13785 · Cited by 3
Retracted
Causal effects of genetically determined blood metabolites on asthma: a bidirectional Mendelian randomization study
Lin, L., Wu, Z., Zhong, A., Luo, H., Xu, W., & Luo, W. (2024) · Journal of Asthma · doi:10.1080/02770903.2024.2380515 · Cited by 3
“Conversely, the random-effects model was employed if substantial heterogeneity was present ( p 0.05) (24).”
Influential
The relationship between lipoproteins and the risk of esophageal cancer: a Mendelian randomization study
Cui, J., Zhang, R., & Li, L. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1432289 · Cited by 3
Genetically predicted HLA-DR+ natural killer cells as potential mediators in the lipid-coronary artery disease/ calcification (CAD/CAC) causal pathway
Qian, D., Zhang, H., Liu, R., & Ye, H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1408347 · Cited by 4
“Directional horizontal pleiotropy may confound causal inference, although MR-Egger regression tests indicate minimal bias (14, 31, 32).”
Background
Evaluating the causal relationship of Levo-carnitine and risk of schizophrenia: a bidirectional two-sample mendelian randomization study
Qiu, H., Zhong, Z., Wu, T., Hu, H., Zhou, M., & Feng, Z. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-06177-1 · Cited by 3
“Detailed information on each data-set is provided in Table S1 [26].”
Background
Causal relationships of familial hypercholesterolemia with the risk of multiple vitamin deficiencies: a Mendelian randomization study
Zhang, C., Wei, G., Zhou, H., & Liu, L. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1401260 · Cited by 3
Identification of Causal Genes and Potential Drug Targets for Restless Legs Syndrome: A Comprehensive Mendelian Randomization Study
Qian, R., Zhao, X., Lyu, D., Xu, Q., Yuan, K., Luo, X., Wang, W., Wang, Y., Liu, Y., Cheng, Y., et al. (2024) · Pharmaceuticals · doi:10.3390/ph17121626 · Cited by 3
Association between Plasma Metabolite Levels and Myopia: A 2-Sample Mendelian Randomization Study
Jiang, X., Xu, B., Li, Q., & Zhao, Y.-E. (2024) · Ophthalmology Science · doi:10.1016/j.xops.2024.100699 · Cited by 3
“The main method, inverse variance weighted (IVW) 13 random-effects models, was used to estimate causal effects when traits were instrumented by 2 or more SNPs. 14 To reduce the risk of false-positive ﬁ ndings, a method based on constrained maximum likelihood and model averaging 15 was also conducted.”
Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study
Guo, A., Chen, P., Cao, J., Wu, C., & Ding, S. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112699 · Cited by 3
“In the bidirectional two-sample MR study, the inverse-variance weighted (IVW) method was the primary analysis approach, offering the highest statistical power (Hemani et al., 2018).”
Causal associations between dietary habits and liver cancer risk: a two-sample Mendelian randomization study
Hu, W., Sun, J., & Liu, C. (2025) · Discover Oncology · doi:10.1007/s12672-025-01885-w · Cited by 3
“To examine the influence of individual single-nucleotide polymorphisms (SNPs), a leave-one-out analysis was conducted, in which one SNP was removed at a time [31].”
Major depressive disorder and the development of cerebral small vessel disease: A Mendelian randomization study
Lu, T., Luo, L., Yang, J., Li, Y., Chen, D., Sun, H., Liao, H., Zhao, W., Ren, Z., Xu, Y. J., et al. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.02.067 · Cited by 3
Multilayer analysis of ethnically diverse blood and urine biomarkers for breast cancer risk and prognosis
Feng, J. F., Qi, X., Chen, C., Li, B., Wang, M., Xie, X., Yang, K., Liu, X., Chen, R. M., Guo, T., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-90447-9 · Cited by 4
“To assess the robustness of significant association identified by IVW, We further conducted sensitivity analyses, including Egger intercept test and MR-PRESSO global test to evaluate horizontal pleiotropy, and LOO analyses to examine the presence of dominant IVs 33,34 .”
Exploring the Relationship Between Antipsychotic Drug Target Genes and Epilepsy: Evidence From Food and Drug Administration Adverse Event Reporting System Database and Mendelian Randomization
Yin, Z., Zhan, Z., Qiu, Y., Wang, M., Li, J., Song, B., Chen, Z., Wu, J., & Wang, Z. (2025) · Brain and Behavior · doi:10.1002/brb3.70467 · Cited by 3
“Meanwhile, the MR-Egger intercept was employed to ascertain whether the findings were influenced by pleiotropy (Hemani et al. 2018).”
Deciphering the influence of socioeconomic status on brain structure: insights from Mendelian randomization
Xia, C., Lu, Y., Zhou, Z., Marchi, M., Kweon, H., Ning, Y., Liewald, D. C. M., Anderson, E. L., Koellinger, P., Cox, S. R., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03047-4 · Cited by 6
“The replication samples are available on request from the Social Science Genetic Association Consortium (https://www.thessgac.org/).”
Exploring the Causal Association Between 91 Circulating Inflammatory Proteins and Neurodegenerative Diseases: A Bidirectional Two‐Sample Mendelian Randomization and Bioinformatics Analysis
Gong, Z., Cao, R., & Zhu, H. (2025) · Brain and Behavior · doi:10.1002/brb3.70586 · Cited by 3
“A statistically significant intercept ( p < 0.05) suggests that SNPs influence outcomes through non-exposure pathways, violating MR’s core assumptions (Hemani et al. 2018).”
Influential
Causal effect of mitochondrial function on psoriasis: A Mendelian randomization study
Huo, Y. P., Chang, C. J., Chen, Y., Lu, P., Huang, Y. K., Lee, T. C., Lin, M. Y., & Chen, C. (2025) · Dermatologica Sinica · doi:10.4103/ds.ds-d-25-00013 · Cited by 3
Causal association of cognitive reserve on Alzheimer's disease with putative sex difference
Wang, H., Rosenthal, S. B., Makowski, C., Lo, M., Andreassen, O. A., Salem, R. M., McEvoy, L. K., Fiecas, M. J. A., & Chen, C. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12270 · Cited by 3
The causal effect of adiposity on hospital costs: Mendelian Randomization analysis of over 300,000 individuals from the UK BiobankPreprint
Dixon, P., Hollingworth, W., Harrison, S., Davies, N. M., & Smith, G. D. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/589820 · Cited by 3
“A number of methods have been developed to accommodate violations of the exclusion restriction due to pleiotropy that is suggested by (but not necessarily unambiguously identified by) high heterogeneity as indicated by Cochran’s Q (62, 63).”
Method
Combining multivariate genomic approaches to elucidate the comorbidity between ASD and ADHDPreprint
Peyre, H., Schoeler, T., Liu, C.-Y., Williams, C. M., Hoertel, N., Havdahl, A., & Pingault, J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.22.054825 · Cited by 3
“We additionally applied MR-Egger regression (45,46) to estimate the intercept 155 (corresponding to a test of directional pleiotropy) in addition to the slope in the regression.”
Method
Neuropsychiatric disorders as risk factors and consequences of COVID-19: A Mendelian randomization studyPreprint
Xiang, Y., Qiu, J., Zhang, R., Chau, C. K., Rao, S., & So, H. (2021) · medRxiv · doi:10.1101/2021.06.29.21259609 · Cited by 3
Evaluation of the causal associations between brain imaging-derived phenotypes and type 2 diabetes: a bidirectional Mendelian randomization studyPreprint
Dong, S., Yu, K., Tang, S.-H., Guo, J., Guo, Y., & Yang, T. (2022) · medRxiv · doi:10.1101/2022.12.16.22283558 · Cited by 3
“estimate the directional pleiotropic effect [40] (P < 0.”
Background
Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHDPreprint
Spychala, K. M., Friedman, N. P., & Gizer, I. R. (2024) · medRxiv · doi:10.1101/2024.06.10.24308620 · Cited by 3
“While this heterogeneity could suggest a violation of the horizontal pleiotropy assumption of MR among one or all instrumental SNPs, heterogeneity can also occur for other reasons, including the heterogeneity tests being biased towards false positives (Hemani, Bowden, et al., 2018).”
Background
Exploring the role of nicotine and smoking in sleep behaviours: A multivariable Mendelian Randomisation studyPreprint
Page, S., Gibson, M., Munafo, M. R., Khouja, J. N., & Richmond, R. C. (2024) · medRxiv · doi:10.1101/2024.08.01.24311349 · Cited by 3
“A non-zero intercept term in MR-Egger regression term is interpreted as the directional pleiotropic effect (Hemani et al., 2018).”
Background
Bridging sleep with psychiatric disorders through genetics
Zimmerman, A. J., & Grant, S. F. A. (2024) · SLEEP · doi:10.1093/sleep/zsae235 · Cited by 3
Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients
Yuan, Z., Lei, W., Xing, X., He, X., Huang, X., Wei, L., Lv, Y., Qiu, S., Yuan, Z., Wang, J., et al. (2024) · BMC Pulmonary Medicine · doi:10.1186/s12890-024-02974-2 · Cited by 2
“To identify potential pleiotropy and assess the robustness of our results, we conducted several analyses, including Cochran’s Q statistic [25] and MR‒Egger intercept tests [21].”
Method
Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration
Kresge, H. A., Blostein, F., Goleva, S. B., Albiñana, C., Revez, J. A., Wray, N. R., Vilhjálmsson, B. J., Zhu, Z., McGrath, J. J., & Davis, L. K. (2024) · Twin Research and Human Genetics · doi:10.1017/thg.2024.19 · Cited by 2
“Of particular interest, our findings lend weight to the hypothesis that variants associated with 25OHD are horizontally (or biologically) pleiotropic (Hemani et al., 2018), and influence 25OHD concentration among other biological functions, such as lipid pathways.”
Background
Hypothyroidism and dermato/polymyositis: a two-sample Mendelian randomization study
Li, Q., Yang, S., Ma, Y., Huang, H., Zhi, L., Wang, S., & Lu, L. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1361581 · Cited by 2
“…MR groups SNPs into clusters and calculates an estimate based on the cluster with the most SNPs. MR-Egger, weighted median, and weighted mode are alternative MR methods that are more robust to directional pleiotropy and were used to calculate estimates for comparison with the IVW estimates (21).”
Method
Role of blood lipids in mediating the effect of dietary factors on gastroesophageal reflux disease: a two-step mendelian randomization study
Liu, X., Han, Y., Yan, G., & Sun, M. (2024) · European Journal of Nutrition · doi:10.1007/s00394-024-03491-y · Cited by 3
“Moreover, the leave-one-out analysis was used to investigate whether the causal relationship between dietary factors, blood lipids and GERD was influenced by a sin - gle SNP [ 69 ].”
Investigating the relationship between blood metabolites and diabetic retinopathy using two-sample mendelian randomization and in vivo validation
Zeng, Y., Mo, G., Wang, X., Yang, Y., Dong, Y., Zhong, R., & Tian, N. (2024) · Scientific Reports · doi:10.1038/s41598-024-73337-4 · Cited by 2
“In the absence of horizontal pleiotropy or in the presence of equilibrium, IVW (fixed effects) methods provide unbiased estimates 15 .”
Evaluating causal associations of chronotype with pregnancy and perinatal outcomes and its interactions with insomnia and sleep duration: a mendelian randomization study
Yang, Q., Magnus, M. C., Kilpi, F., Santorelli, G., Soares, A. G., West, J., Magnus, P. M., Håberg, S. E., Tilling, K. M., Lawlor, D. A., et al. (2024) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-024-07023-8 · Cited by 3
A causal link between circulating immune cells and erectile dysfunction: Two-sample bidirectional Mendelian randomization study
Wu, G., Wang, J., Zhu, W., Liu, H., Ding, W., Liu, Y., Wang, Z., & Tao, L. (2024) · Medicine · doi:10.1097/md.0000000000041124 · Cited by 2
Causal association between genetically predicted primary aldosteronism and aortic aneurysm and aortic dissection: A Mendelian randomization study
Liu, S., Wan, J., Yang, Y., Wang, D., Hou, J., & Wang, P. (2025) · Medicine · doi:10.1097/md.0000000000041951 · Cited by 2
“[24] 28] Among these methodologies, IVW was designated as the principal approach for evaluating effect estimates, taking heterogeneity into account.”
Decoding the causal association between immune cells and three chronic respiratory diseases: Insights from a bi-directional Mendelian randomization study
Xie, A., Zhao, H., Song, C., Wang, R., Wu, L., Chen, R., Jiang, G., Liu, W. L., Liu, J., & Mao, W. (2025) · BMC Pulmonary Medicine · doi:10.1186/s12890-025-03641-w · Cited by 2
“Furthermore, heterogeneity has been estimated utilizing Cochrane’s Q test, which represents no heterogeneity present when P > 0.05 [27].”
Influential
Exploring Therapeutic Targets for Age-Related Macular Degeneration From Circulating Proteins to Plasma Metabolites in the European Population
Chen, C., Lan, Y., Yan, W., Zhang, X., Li, T., & Han, J. Y. (2025) · Translational Vision Science & Technology · doi:10.1167/tvst.14.5.8 · Cited by 2
“32,44 The HEIDI test was employed to identify linkage disequilibrium between circulating proteins and AMD in SMR. 45 The MR-Egger intercept test and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) global test were further performed to find potential pleiotropy in…”
Mendelian Randomization Assessment of the Genetic Effects of Lipid‐Lowering Drugs on Digestive System Cancers
Ma, K., Wang, H., Du, Y., Chen, T., Yang, D., Li, Y., & Li, D. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.70293 · Cited by 2
“We used MR-Egger intercept and pleiotropic residuals and outliers (MR-PRESSO) to assess horizontal pleiotropy, and the p - value less than 0.05 indicated the presence of horizontal pleiotropy (Hemani et al. 2018).”
Influential
Causal relationship between inflammatory bowel disease and cardiovascular disease: a two-sample Mendelian randomized study
Ma, L., Ding, L., Xing, Z., Ren, H., Wei, J., Song, H., Qiu, B., Chen, Z., & Wang, Y. (2025) · Archives of Medical Science · doi:10.5114/aoms/204370 · Cited by 2
“If the Egger-intercept was close to 0 or there was no statistical significance, it indicated that there was no genetic plei-otropy [14].”
Mediating role of thyroid dysfunction in the relationship between insomnia and osteoporosis: A Mendelian randomization analysis
Wu, L., Zhang, H., Li, Y., Tang, J., wang, D., & Zhu, L. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112842 · Cited by 2
“We applied the MR-PRESSO method to detect and exclude outliers, as their presence indicates horizontal pleiotropy (Hemani et al., 2018).”
ZDHHC5 Mediates Immune Dysregulation Driving Generalized Anxiety Disorder Risk
Fuqiang, S., Lu, G., Li, N., Dai, K., Ren, Z., Ma, R., Feng, Y., Zong, S., & Cheng, B. (2025) · Brain and Behavior · doi:10.1002/brb3.70818 · Cited by 3
“A non-significant intercept ( p > 0.05) was interpreted as evidence for the absenceofsubstantialhorizontalpleiotropyintheMRframework (Hemani et al. 2018, Zou et al. 2021).”
Influential
Lipid metabolism and osteonecrosis: unraveling causal mechanisms via multi-omics and mendelian randomization
Chen, Y., Zhou, Z., Che, H., & Ding, L. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1642153 · Cited by 3
From Gene to Scar: Proteome-Wide Causal Insights into Keloid Pathogenesis and Prevention
Xu, Y., Liu, J.-C., Jiang, Z., Zhang, J., He, R., Wan, M., & Zhao, S. (2025) · Advances in Wound Care · doi:10.1177/21621918251387987 · Cited by 2
“27 After the analysis was completed, the leave-one-out test was used to further evaluate the robustness of the results.”
Follistatin levels and endocrine disorders: A two-sample Mendelian randomization study
Zhang, W. D., Wu, T., Zhao, X., Ma, Y., & Han, X. (2025) · Medicine · doi:10.1097/md.0000000000045566 · Cited by 2
“Open datasets of genetic variants and disease information simplify implementation and avoid ethical constraints, making MR studies more viable than RCTs. [16,17] Given the unique advantages of MR, we conducted a 2-sample MR analysis using GWAS summary data from the UK Biobank and Finnish databases.”
Causal Relationships between 1400 Serum Metabolite Traits,179 Plasma Lipids, and Hemorrhoids: A Mendelian Randomization Study and Meta-analysis
Hu, L., Wang, D., You, C., Zhao, Z., Zheng, W., Wang, L., Li, Y., Dai, L., & Yu, H. (2025) · Life Conflux · doi:10.71321/8s70we60 · Cited by 2
“For the MR-Egger regression intercept, a P > 0.05 suggested that horizontal pleiotropy could be ignored [26].”
Influential
Association of female reproductive traits with altered aging trajectories: Insights from genetic and observational analyses
Lou, C., Wang, G., Xiong, Z., Jiang, Y. C., Li, Y., Zhu, M. Q., Yang, H., Wang, L., He, L., Chang, H., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102481 · Cited by 2
Understanding Mendelian Randomization
Bentz, G. P., & Lambrechts, M. J. (2025) · Clinical Spine Surgery A Spine Publication · doi:10.1097/bsd.0000000000002014 · Cited by 2
Artemisinin exerts anti-inflammatory effects in osteoarthritis through the inhibition of TGF-β1 signaling
Zheng, X., Yu, B., Song, Y., Chen, Y., Li, Z., & Yao, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1717045 · Cited by 2
The association between remnant cholesterol and cardiovascular events: A systematic review and meta-regression
Byrne, P., Lin, T., Jones, M., Demasi, M., Saif-Ur-Rahman, K., & DuBroff, R. J. (2026) · Journal of clinical lipidology · doi:10.1016/j.jacl.2026.03.026 · Cited by 2
DNA Methylation Regulates CDK5R1 and NRBP1 to Exert Effects on Alcohol Dependence: Insights From Mendelian Randomization
Deng, F.-Y., Peng, J., Lai, S.-R., Zhang, G.-P., Li, M.-M., Huang, Y.-X., Yuan, M., Yao, G., Zhang, P., & Lu, L.-M. (2026) · Addiction Biology · doi:10.1111/adb.70162 · Cited by 2
Integrative analyses elucidate transcriptional regulatory functions of risk alleles for metabolic liver disease
Zhu, B., He, N., Xiao, Y., Chen, B., Li, C., Mandla, R., Liu, Y., Zhang, J., Chang, X., Yu, F., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02617-8 · Cited by 4
“We observed that rs474513 affects the expression of SLC22A3 and LPA in the opposite directions, demonstrating how a single variant can disparately regulate multiple genes 55 .”
Inflammatory protein mediators linking gut microbiota to degenerative lumbar spine disorders: cross-disease genetic evidence
Lou, Y., Ma, D., Gan, Q., 許先越, Xiao, Y., Wang, J., Li, Z., Zhang, T., Qi, L., & Feng, S. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1855966 · Cited by 2
“Furthermore, the qPCR results were not entirely consistent with MR ﬁ ndings, likely due to differences between long-term genetic effects and tissue-speci ﬁ c expression under pathological conditions (31).”
The Effects of Fatty Acids on Primary Liver Cancer: A Two-Sample Mendelian Randomization Study
Liu, Y., He, J., Cai, L., & Leng, A. (2023) · Nutrition and Cancer · doi:10.1080/01635581.2023.2216914 · Cited by 2
“the fixed-effects method was used (40).”
Causal relationship between circulating vitamin C and 25-hydroxyvitamin D concentrations and common mental disorders - a Mendelian randomization study
Wang, Y., Dong, L., Zhao, M., Yin, S., Da, P., Xu, D., Lü, Y., Xia, J., Wang, N., Wang, S., et al. (2023) · Food Science and Human Wellness · doi:10.26599/fshw.2022.9250156 · Cited by 2
Causal Association Between Tea Consumption and Gout: A Mendelian Randomization Study
Wang, Q., Liu, Y., Zhang, H., Zhang, Z., Huang, X.-Y., & Xiao, W. (2023) · Current Medical Science · doi:10.1007/s11596-023-2778-6 · Cited by 2
“Alternatively, we used a random-effects model [40] .”
Method

Authors: Hemani, G., Bowden, J., & Davey Smith, G.
Affiliations: University of Bristol (GB)
MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol
Corresponding author: Hemani, Gibran
ORCID: Hemani, Gibran
Bowden, Jack
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 2018-05-16
Volume: 27
Issue: R2
Pages: R195-R208
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/ddy163
PMC: PMC6061876
OpenAlex: W2810852503
Cited by: 1,496
References: 113
Citations by year: 2026: 129 · 2025: 266 · 2024: 422 · 2023: 209 · 2022: 169 · 2021: 131 · 2020: 101 · 2019: 62 · 2018: 7
FWCI: 10.71
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Human Molecular Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Bristol Research (University of Bristol) (submittedVersion, cc-by)
Funders: Wellcome Trust (208806/Z/17/Z)
Medical Research Council (MC_UU_12013/1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords: pleiotropy, Mendelian randomization, horizontal pleiotropy, single nucleotide polymorphisms, causal inference, phenome-wide association study, genetic variants
MeSH terms: Animals, Humans, Phenotype, Genetic Variation, Reproducibility of Results, Genome, Human, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis, Genetic Pleiotropy

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Evaluating the potential role of pleiotropy in Mendelian randomization studies

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks