The DOI matches its Crossref record; 38 of the 40 references it cites were found in a registry or an index.
Association of Lipid Fractions With Risks for Coronary Artery Disease and Diabetes
Open accessAbstract
IMPORTANCE: Low-density lipoprotein cholesterol (LDL-C) is causally related to coronary artery disease (CAD), but the relevance of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) is uncertain. Lowering of LDL-C levels by statin therapy modestly increases the risk of type 2 diabetes, but it is unknown whether this effect is specific to statins. OBJECTIVE: To investigate the associations of 3 routinely measured lipid fractions with CAD and diabetes through mendelian randomization (MR) using conventional MR and making use of newer approaches, such as multivariate MR and MR-Egger, that address the pleiotropy of genetic instruments where relevant. DESIGN, SETTING, AND PARTICIPANTS: Published data from genome-wide association studies were used to construct genetic instruments and then applied to investigate associations between lipid fractions and the risk of CAD and diabetes using MR approaches that took into account pleiotropy of genetic instruments. The study was conducted from March 12 to December 31, 2015. MAIN OUTCOMES AND MEASURES: Coronary artery disease and diabetes. RESULTS: Genetic instruments composed of 130 single-nucleotide polymorphisms (SNPs) were used for LDL-C (explaining 7.9% of its variance), 140 SNPs for HDL-C (6.6% of variance), and 140 SNPs for TGs (5.9% of variance). A 1-SD genetically instrumented elevation in LDL-C levels (equivalent to 38 mg/dL) and TG levels (equivalent to 89 mg/dL) was associated with higher CAD risk; odds ratios (ORs) were 1.68 (95% CI, 1.51-1.87) for LDL-C and 1.28 (95% CI, 1.13-1.45) for TGs. The corresponding OR for HDL-C (equivalent to a 16-mg/dL increase) was 0.95 (95% CI, 0.85-1.06). All 3 lipid traits were associated with a lower risk of type 2 diabetes. The ORs were 0.79 (95% CI, 0.71-0.88) for LDL-C and 0.83 (95% CI, 0.76-0.90) for HDL-C per 1-SD elevation. For TG, the MR estimates for diabetes were inconsistent, with MR-Egger giving an OR of 0.83 (95%CI, 0.72-0.95) per 1-SD elevation. CONCLUSIONS AND RELEVANCE: Routinely measured lipid fractions exhibit contrasting associations with the risk of CAD and diabetes. Increased LDL-C, HDL-C, and possibly TG levels are associated with a lower risk of diabetes. This information will be relevant to the design of clinical trials of lipid-modifying agents, which should carefully monitor participants for dysglycemia and the incidence of diabetes.
Overview
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
Cites
Statistics
Verification
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?
In the citing paper
“as pharmacological modification of C-reactive protein is unlikely to be beneficial to CHD 51 , whereas randomized evidence demonstrates the value of targeting biomarkers further upstream, e.g. interleukin-6 receptor 21,54 or interleukin 1-beta 52”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [21]
In the citing paper
“With increasing availability of large-scale phenotyping (and genotyping), MR is being widely applied to quantitative traits (e.g. markers or adiposity, such as body mass index 13-16 ; blood lipids such as HDL-cholesterol 17-19 ; inflammation-related proteins such as interleukin-6 receptor 20,21 12 ) with the aim of discovering modifiable risk factors for disease that are causal and amenable to the”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [21]
In the citing paper
“In this latter example, genetic variants used to mimic pharmacological inhibition of IL6R (and thus the effects of inhibiting pathways downstream of IL6) lead to a paradoxical increase in IL6 concentrations in the blood 21 ,”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [21]
In the citing paper
“Exploring inflammation-related proteins more upstream, genetic variants around the gene encoding interleukin 6 receptor (IL6R) shows an association with risk of CHD 21,54 .”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [21]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bowden, J., Davey Smith, G., & Burgess, S. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv080 · Cited by 9,816
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology
Lawlor, D. A., Harbord, R. M., Sterne, J. A. C., Timpson, N., & Davey Smith, G. (2008) · Statistics in Medicine · doi:10.1002/sim.3034 · Cited by 4,618
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487
Self-citationWiller (2013) · doi:10.1038/ng.2797 · Cited by 2,983
Collaborators, C. T. T. (. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60367-5 · Cited by 2,833
Effects of dalcetrapib in patients with a recent acute coronary syndrome
Schwartz, G. G., Olsson, A. G., Abt, M., Ballantyne, C. M., Barter, P. J., Brumm, J., Chaitman, B. R., Holme, I. M., Kallend, D., Leiter, L. A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1206797 · Cited by 2,022
the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segrè, A. V., Steinthorsdottir, V., Strawbridge, R. J., Khan, H., Grallert, H., et al. (2012) · Nature Genetics · doi:10.1038/ng.2383 · Cited by 1,912
Calculating statistical power in Mendelian randomization studies.
Brion, M.-J. A., Shakhbazov, K., & Visscher, P. M. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dyt179 · Cited by 1,751
Large-scale association analysis identifies new risk loci for coronary artery disease
The CARDIoGRAMplusC4D Consortium, Deloukas, P., DIAGRAM Consortium, CARDIOGENICS Consortium, MuTHER Consortium, Wellcome Trust Case Control Consortium, Kanoni, S., Willenborg, C., Farrall, M., Assimes, T. L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2480 · Cited by 1,614
Cited by
Sorted by citations
Items 101–200 of 296
Evaluation of the Pleiotropic Effects of Statins
Labos, C., Brophy, J. M., Smith, G. D., Sniderman, A. D., & Thanassoulis, G. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.310052 · Cited by 36
Porcu, E., Gilardi, F., Darrous, L., Yengo, L., Bararpour, N., Gasser, M., Marques-Vidal, P. M., Froguel, P., Waeber, G., Thomas, A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-85684-7 · Cited by 33
Effect of bempedoic acid on new onset or worsening diabetes: a meta-analysis
Masson, W., Lobo, M., Lavalle-Cobo, A., Masson, G., & Molinero, G. (2020) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2020.108369 · Cited by 34
Maki, K. C., Palacios, O. M., Lindner, E., Nieman, K. M., Bell, M., & Sorce, J. (2017) · Journal of Nutrition · doi:10.3945/jn.117.248641 · Cited by 36
A genetic risk score for fasting plasma glucose is independently associated with arterial stiffness
Gottsäter, M., Hindy, G., Orho‐Melander, M., Nilsson, P. M., & Melander, O. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001646 · Cited by 34
From lipid locus to drug target through human genomics
van der Laan, S. W., Harshfield, E. L., Hemerich, D., Stacey, D., Wood, A., & Asselbergs, F. W. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy120 · Cited by 33
Self-citationHigh-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity
Denimal, D., Monier, S., Bouillet, B., Vergès, B. L., & Duvillard, L. (2023) · Metabolites · doi:10.3390/metabo13020253 · Cited by 35
Chang, X., Zhao, Z., Zhang, W., Liu, D., Ma, C., Zhang, T., Meng, Q., Yan, P., Zou, L., & Ming, Z. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6620677 · Cited by 34
“FFAs can escape from adipocytes into the blood and accumulate heterotopically in nonadipocytes, causing lipid toxicity [191, 192].”
BackgroundRetractedFiorentino, T. V., Succurro, E., Marini, M. A., Pedace, E., Andreozzi, F., Perticone, M., Sciacqua, A., Perticone, F., & Sesti, G. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3289 · Cited by 33
“Conversely, genetic studies exploring the relationship between type 2 diabetes and genetic variants linked to reduced HDL-C levels have provided conflicting results, thus arguing against the causal relationship between low levels of HDL-C and type 2 diabetes.(23-25) Moreover, although a longitudinal association betwee…”
ResultDalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease
Schwartz, G. G., Leiter, L. A., Ballantyne, C. M., Barter, P. J., Black, D. M., Kallend, D. G., Laghrissi‐Thode, F., Leitersdorf, E., McMurray, J. J. V., Nicholls, S. J., et al. (2020) · Diabetes Care · doi:10.2337/dc19-2204 · Cited by 34
Self-citationLi, H., Zhang, Q., Shen, W., Li, B., Lv, W., Xiao, H., & Deng, H. (2020) · Aging · doi:10.18632/aging.102815 · Cited by 34
Cumulative burden of lipid profiles predict future incidence of ischaemic stroke and residual risk
Dai, L., Xu, J., Zhang, Y., Wang, A., Chen, Z., Mo, J., Li, H., Meng, X., Wu, S., & Wang, Y. (2021) · Stroke and Vascular Neurology · doi:10.1136/svn-2020-000726 · Cited by 33
Li, S., Guo, Y., Zhao, X., Zhang, Y., Zhu, C., Wu, N., Xu, R., Qing, P., Gao, Y., Li, X., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-00499-9 · Cited by 32
Gordillo‐Marañón, M., Zwierzyna, M., Charoen, P., Drenos, F., Chopade, S., Shah, T., Engmann, J., Casas, J. P., Chaturvedi, N., Papacosta, O., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25731-z · Cited by 32
“As a positive control step, our (genome-wide) biomarker MR analysis replicated previous findings on the potential causal relevance of LDL-C, TG, and HDL-C (4, 10, 28).”
Self-citationStrawbridge, R. J., & van Zuydam, N. R. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1021-5 · Cited by 31
Haynes, R., Valdés‐Márquez, E., Hopewell, J. C., Chen, F., Li, J., Parish, S., Landray, M., Armitage, J., Haynes, R., Valdés‐Márquez, E., et al. (2019) · Clinical Therapeutics · doi:10.1016/j.clinthera.2019.06.012 · Cited by 30
Joshi, R., Wannamethee, S. G., Engmann, J., Gaunt, T. R., Lawlor, D. A., Price, J. F., Papacosta, O., Shah, T., Tillin, T., Chaturvedi, N., et al. (2020) · European Journal of Preventive Cardiology · doi:10.1177/2047487319899621 · Cited by 30
Self-citationCausal Effect of Lipids and Lipoproteins on Atherosclerosis
Ference, B. A. (2018) · Cardiology Clinics · doi:10.1016/j.ccl.2017.12.001 · Cited by 28
The evolving role of cholesteryl ester transfer protein inhibition beyond cardiovascular disease
Mehta, N. N., Dangas, K., Ditmarsch, M., Rensen, P. C. N., Dicklin, M. R., & Kastelein, J. J. P. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106972 · Cited by 28
Familial Hypercholesterolemia and Type 2 Diabetes in the Old Order Amish
Xu, H., Ryan, K. A., Jaworek, T. J., Southam, L., Reid, J. G., Overton, J. D., Baras, A., Puurunen, M. K., Zeggini, E., Taylor, S. I., et al. (2017) · Diabetes · doi:10.2337/db17-0173 · Cited by 28
“Given these possibilities, Mendelian randomization studies that have shown genetic risk scores for high LDL-C to be inversely correlated with T2D risk (2,19,20) should be interpreted cautiously, as the risk score–driving risk alleles included in these analyses typically fall in a range of different genes and their eff…”
BackgroundRath, A. A., Lam, H. S., & Schooling, C. M. (2021) · European Journal of Clinical Nutrition · doi:10.1038/s41430-021-00882-w · Cited by 28
Siewert, K. M., & Voight, B. F. (2018) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.118.002239 · Cited by 28
Schorr, K., Agayn, V., de Groot, C. P. G. M., Slagboom, P. E., & Beekman, M. (2024) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2024.100272 · Cited by 30
Khaloo, P., Hasheminia, M., Tohidi, M., Abdi, H., Mansournia, M. A., Azizi, F., & Hadaegh, F. (2018) · Nutrition & Metabolism · doi:10.1186/s12986-018-0287-6 · Cited by 27
Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism
González-Lleó, A. M., Sánchez-Hernández, R. M., Boronat, M., & Wägner, A. M. (2022) · Nutrients · doi:10.3390/nu14071503 · Cited by 31
Schmidt, A. F., Joshi, R., Gordillo‐Marañón, M., Drenos, F., Charoen, P., Giambartolomei, C., Bis, J. C., Gaunt, T. R., Hughes, A. D., Lawlor, D. A., et al. (2023) · Communications Medicine · doi:10.1038/s43856-022-00234-0 · Cited by 30
Self-citationLiu, H., Li, J., Liu, F., Huang, K., Cao, J., Chen, S., Li, H., Shen, C., Hu, D., Huang, J., et al. (2023) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwad111 · Cited by 26
Li, B., Liu, Y., Zhou, X. J., Chen, L., Yan, L., Tang, X., Gao, Z., Wan, Q., Luo, Z., Qin, G., et al. (2024) · Journal of Diabetes · doi:10.1111/1753-0407.13592 · Cited by 27
“54 Moreover, it has been described that high RC increases the risk of atherosclerosis also among people having normal TG values.”
BackgroundCardioprotective Properties of HDL: Structural and Functional Considerations
Pappa, E. T., Elisaf, M., Kostara, C. E., Bairaktari, E. T., & Tsimihodimos, V. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190201142321 · Cited by 28
HDL in Morbidity and Mortality: A 40+ Year Perspective
Tall, A. R. (2020) · Clinical Chemistry · doi:10.1093/clinchem/hvaa148 · Cited by 26
“Multivariate MR of lipid traits in CHD using larger CHD datasets also detected an HDL-C association, but this association became nonsignificant after mathematical modeling of unmeasured pleiotropy; the TG relationship was also attenuated but remained significant (12).”
BackgroundChen, J., Li, R., Geng, T., Wang, Y., Lu, Q., Tu, Z., Li, Y., Liao, Y.-F., Yang, K., Zhou, L., et al. (2023) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwad053 · Cited by 26
Smit, R. A. J., Trompet, S., Leong, A., Goodarzi, M. O., Postmus, I., Warren, H. R., Theusch, E., Barnes, M. R., Arsenault, B. J., Li, X., et al. (2019) · The Pharmacogenomics Journal · doi:10.1038/s41397-019-0125-x · Cited by 26
Emerging Targets for Cardiovascular Disease Prevention in Diabetes
Stitziel, N. O., Kanter, J. E., & Bornfeldt, K. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.011 · Cited by 28
Lee, Y., Kim, Y. A., & Seo, J. H. (2022) · Genes · doi:10.3390/genes13122407 · Cited by 25
“95 from MR-Egger) [48], consistent with our findings.”
BackgroundResultJiang, H., Si, M., Tian, T., Shi, H., Huang, N., Chi, H., Yang, R. J., Long, X., & Qiao, J. (2023) · European journal of medical research · doi:10.1186/s40001-023-01174-8 · Cited by 25
“As an instrumental variable method investigating the causal effects of traits using genetic predictors, MR has been used to determine the causal paths among glucose, insulin, and lipid metabolism markers in humans [24, 25, 44, 45].”
MethodSun, S., Jiao, M., Han, C., Zhang, Q., Shi, W., Shi, J., & Li, X. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00621 · Cited by 23
Xu, Q., Chen, C., You, R., Ni, L., Chen, S., & Peng, B. (2023) · BMC Medical Genomics · doi:10.1186/s12920-023-01625-5 · Cited by 21
“…regression model coefficients could be used to estimate an unbiased causal effect of exposure on the outcome by satisfying merely the assumption that IV’s direct effect on outcome was independent of IV’s association with exposure (instrument strength independent of direct effect, InSIDE) [13].”
MethodPatil, S. P., Rojulpote, C., Gonuguntla, K., Karambelkar, P., Bhattaru, A., Raynor, W., Borja, A. J., Vuthaluru, K., Zhang, V., Werner, T. J., et al. (2020) · PubMed Central · Cited by 23
He, L., Culminskaya, I. V., Loika, Y., Arbeev, K. G., Bagley, O., Duan, M., Yashin, A. I., & Kulminski, A. M. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.09.019 · Cited by 22
“Recent MR studies using MR-Egger (Bowden et al., 2015; White et al., 2016) find that increased LDL-C levels are associated with lower risk of T2D, which is consistent with our results.”
The therapeutic potential of CETP inhibitors: a patent review
Wang, X., Li, W., Hao, L., Xie, H., Hao, C., Liu, C., Li, W., Xiong, X., & Zhao, D. (2018) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2018.1439476 · Cited by 22
Hsu, L., Teng, M., Wu, S., Chou, H., & Ko, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810418 · Cited by 21
“Previous studies including GWAS and MR analyses have demonstrated that a genetically induced elevation of circulated LDL-C levels is associated with a lower risk of DM [12,46], supporting the observation that lowering LDL-C levels with statins slightly increases the risk of DM [13–16].”
ResultMendelian randomization studies on coronary artery disease: a systematic review and meta-analysis
Silva, S., Fatumo, S., & Nitsch, D. (2024) · Systematic Reviews · doi:10.1186/s13643-023-02442-8 · Cited by 24
Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis
Kamran, H., Kupferstein, E., Sharma, N., Karam, J. G., Myers, A. K., Youssef, I., Sowers, J. R., Gustafson, D., Salifu, M. O., & McFarlane, S. I. (2018) · Cardiorenal Medicine · doi:10.1159/000485196 · Cited by 22
Effect of berries/apple mixed juice consumption on the positive modulation of human lipid profile
Habánová, M., Saraiva, J. A., Holovičová, M., Moreira, S. A., Fidalgo, L. G., Habán, M., Gažo, J., Schwarzová, M., Chlebo, P., & Bronkowska, M. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103417 · Cited by 22
A two-sample Mendelian randomization study explores metabolic profiling of different glycemic traits
Wong, T. H. T., Mo, J. M. Y., Zhou, M., Zhao, J. V., Schooling, C. M., He, B., Luo, S., & Yeung, S. L. A. (2024) · Communications Biology · doi:10.1038/s42003-024-05977-1 · Cited by 21
“Third, there were signs of reverse causation for lipids related traits after correcting for multiple comparisons, which were consistent with previous Mendelian randomization studies 56,57 .”
ResultPCSK9 inhibition: the dawn of a new age in cholesterol lowering?
Preiss, D., & Mafham, M. (2016) · Diabetologia · doi:10.1007/s00125-016-4178-y · Cited by 21
“In addition, it is well recognised that PCSK9 inhibition leads to a reduction in levels of lipoprotein(a), an atherogenic lipid particle causally implicated in CVD [23], of about 20–30% [24, 25].”
BackgroundResultInfluentialSelf-citationUnexplained reciprocal regulation of diabetes and lipoproteins
Higuchi, S., Izquierdo, M. C., & Haeusler, R. A. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000521 · Cited by 20
High-Density Lipoprotein in Patients with Diabetic Kidney Disease: Friend or Foe?
Liu, K., Cooper, M. E., Chai, Z., & Liu, F. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041683 · Cited by 20
“Mendelian randomization studies also suggest a negative correlation between HDL-C and T2D risk [159,160], and high HDL-C levels potentially offer protection against DKD [161].”
Ahmad, S., Mora, S., Ridker, P. M., Hu, F. B., & Chasman, D. I. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311562 · Cited by 19
Sacks, F. M., Furtado, J. D., & Jensen, M. K. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159182 · Cited by 19
Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol
Mohamed, F., Mansfield, B. S., & Raal, F. J. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12155082 · Cited by 20
“However, the causal nature of low HDL-C in ASCVD remains unclear, with conflicting results from various Mendelian randomization studies [36].”
Liu, Y., Ettinger, A. S., Téllez‐Rojo, M. M., Sánchez, B. N., Zhang, Z., Cantoral, A., Hu, H., & Peterson, K. E. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz038 · Cited by 18
Yang, G., & Schooling, C. M. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01714-2 · Cited by 17
“Previous studies investigating the associations of TG and Lp(a) with type 2 diabetes risk have yielded contradictory results, suggesting inverse [1, 12], null [13–15] or positive [2, 7, 16] associations of TG, and inverse [17] or null [18] associations of Lp(a).”
BackgroundResultInfluentialLiu, G., Jiang, L., Kerchberger, V. E., Oeser, A. M., Ihegword, A., Dickson, A. L., Daniel, L. L., Shaffer, C. M., Linton, M. F., Cox, N. J., et al. (2023) · Clinical and Translational Science · doi:10.1111/cts.13462 · Cited by 18
Yang, G., & Schooling, C. M. (2023) · BMC Medicine · doi:10.1186/s12916-023-02903-w · Cited by 18
Xie, Y., Liu, S., Wang, X., Huang, H., Wang, M., Qu, W., Yu, Z., Wang, W., & Luo, X. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.123.032409 · Cited by 18
“46 Different from previous studies, we further explored the associations between varied components of serum lipoprotein with 2 characteristic CSVD manifestations (SVS and WMH volume).”
Mei, Z., Xu, L., Huang, Q., Lin, C., Yu, M., Shali, S., Wu, H., Lu, Y., Wu, R., Wang, Z., et al. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.124.036906 · Cited by 17
Dijk, W., & Cariou, B. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13636 · Cited by 19
“Indeed, genetic variation in HMG-CoA reductase and other genes that lower plasma LDL-C levels has been associated with a moderately increased risk of NOD.79,80 Conversely, subjects with FH due to mutations in the LDLR and APOB have a significantly reduced risk to develop T2DM.81 Beyond genetic variation, the LDL-C low…”
BackgroundInfluentialNetwork Mendelian randomization study: exploring the causal pathway from insomnia to type 2 diabetes
Wen, X., Jiating, L., Minjun, X., Li, W., Wu, Q., & Lizhen, L. (2022) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2021-002510 · Cited by 16
Baghbani‐Oskouei, A., Tohidi, M., Asgari, S., Ramezankhani, A., Azizi, F., & Hadaegh, F. (2018) · Intern J Endocrinol Metab · doi:10.5812/ijem.84750 · Cited by 18
“genetic assessment as used in the Mendelian randomization study (37).”
MethodHow Might Bromodomain and Extra-Terminal (BET) Inhibitors Operate in Cardiovascular Disease?
Schooling, C. M., & Zhao, J. V. (2019) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-018-00315-3 · Cited by 17
Yu, C., Chen, S., Zhang, Y.-R., Wang, H.-F., Huang, S., Chen, S., Deng, Y., Wu, B., Kuo, K., Wang, R., et al. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15659 · Cited by 17
“…date, the majority of previous studies only considered the simplified subclassification of lipids or non- lipids, but failed to distinguish among their size, density, or concentrations and specific compositions, which may produce divergent relationships with vascular diseases (Wurtz et al., 2015).”
BackgroundResultFerrières, J., Lautsch, D., Ambegaonkar, B. M., Ferrari, G. M. D., Vyas, A., Baxter, C. A., Bash, L. D., Velkovski-Rouyer, M., Horack, M., Almahmeed, W. A., et al. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.06.008 · Cited by 18
“However, this relationship does not appear to hold true for patients with very high HDL-C levels [28], and data from genome-wide association studies failed to demonstrate an effect of high HDL-C on CHD risk [29].”
ResultCETP inhibition, statins and diabetes
Barter, P. J., Cochran, B. J., & Rye, K. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.09.033 · Cited by 17
In-depth Mendelian randomization analysis of causal factors for coronary artery disease
Tan, Y.-D., Xiao, P., & Guda, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-66027-4 · Cited by 17
Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model
Almowallad, S. J., Huwait, E. A., Al-Massabi, R. F., Saddeek, S., Gauthaman, K., & Prola, A. (2020) · Pharmaceuticals · doi:10.3390/ph13110372 · Cited by 16
“However, a significant issue with its use concerns increased associations with a continued risk of CVD, as well as causing severe, adverse side effects such as diabetes [6] or hemorrhagic stroke [7] in different patient populations.”
BackgroundHolmes, M. V., & Smith, G. D. (2018) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2017.10.006 · Cited by 16
Self-citationMosley, J. D., Feng, Q., Wells, Q. S., Driest, S. L. V., Shaffer, C. M., Edwards, T. L., Bastarache, L. A., Wei, W., Davis, L. K., McCarty, C. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05624-4 · Cited by 16
Effects of Adiponectin on T2DM and Glucose Homeostasis: A Mendelian Randomization Study
Chen, Z., Bai, Y., Long, X., Luo, Q., Wen, Z., Li, Y., Huang, S., Yan, Y., & Mo, Z. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s248352 · Cited by 15
Human genetic insights into lipoproteins and risk of cardiometabolic disease
Stitziel, N. O. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000389 · Cited by 14
Preventing Diabetes and Atherosclerosis in the Cardiometabolic Syndrome
Ahmad, M. I., & Shapiro, M. D. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00913-8 · Cited by 14
Bilgic, S., Pencina, K. M., Pencina, M. J., Cole, J., Dufresne, L., Thanassoulis, G., & Sniderman, A. D. (2024) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.321165 · Cited by 15
HDL and Cholesterol Ester Transfer Protein (CETP)
Deng, S., Liu, J., & Niu, C. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-981-19-1592-5_2 · Cited by 14
Mahrooz, A., Khosravi-Asrami, O. F., Alizadeh, A., Mohmmadi, N., Bagheri, A., Kashi, Z., Bahar, A., Nosrati, M., & Mackness, M. (2023) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2023.05.020 · Cited by 14
Lee, S., Sung, J. M., Cho, I., Kim, H. C., & Chang, H. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195459 · Cited by 14
Chen, Y., Du, M., Xu, J., & Chen, D. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0627-y · Cited by 14
“[17] previously reported that increased LDL cholesterol levels were associated with a lower risk of type 2 diabetes.”
BackgroundGraham, A. (2023) · Biology · doi:10.3390/biology12091232 · Cited by 14
“More recently, the application of multi-variant MR and MR-Egger methodologies, combined with analysis of datasets derived from large genome-wide association studies (GWAS), have indicated the protective effects of HDL-C in reducing the risk of CVD and diabetes [9,10].”
MethodHu, C., Zhou, Y., Wu, X., Jia, X., Zhu, Y., Zheng, R., Wang, S., Lin, L., Qi, H., Lin, H., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04202-7 · Cited by 15
“Findings from a previous MR study [42] suggested that triglycerides may show a causal effect on lowering risk of T2DM, although the effect was marginal.”
BackgroundPrecision Medicine and Cardiovascular Health: Insights from Mendelian Randomization Analyses
Spiller, W., Jung, K. J., Lee, J., & Jee, S. H. (2019) · Korean Circulation Journal · doi:10.4070/kcj.2019.0293 · Cited by 13
Genetic analysis of emerging risk factors in coronary artery disease
van Iperen, E. P. A., Sivapalaratnam, S., Holmes, M. V., Hovingh, G. K., Zwinderman, A. H., & Asselbergs, F. W. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.09.008 · Cited by 12
“More recently, White et al.used 140 SNPs and identi fi ed a consistent causal association of TG with risk of CAD using different MR approaches [57].”
Self-citationZheng, R., & Lind, L. (2024) · Scientific Reports · doi:10.1038/s41598-024-61440-5 · Cited by 11
“Earlier MR studies suggested that genetic variants affecting HDL-cholesterol levels are not associated with CVD risk 16,42 and more recent MR studies also did not strongly support an independent role of HDL in CVD risk 17,19,43 .”
BackgroundInteraction Between Primary Hyperlipidemias and Type 2 Diabetes: Therapeutic Implications
Zubirán, R., Cruz‐Bautista, I., & Aguilar-Salinas, C. A. (2024) · Diabetes Therapy · doi:10.1007/s13300-024-01626-2 · Cited by 11
“C, the risk of T2D was reduced by 21% [R 0.79 (0.71–0.88)), as was the case for 130 SNPs scores every 16 mg/dl esti‑ mated increase in HDL‑c (OR 0.83 (0.76–0.90)] [7].”
BackgroundInfluentialAssociation between different types of plant-based diet and dyslipidaemia in Korean adults
Shin, N., & Kim, J. (2021) · British Journal Of Nutrition · doi:10.1017/s0007114521003482 · Cited by 10
“Dyslipidemia is a well-known risk factors for cardiovascular disease (CVD) coronary heart disease, type 2 diabetes and stroke (1-4) .”
BackgroundZhao, J., Ke, Z., Huang, R., Wen, X., Liu, W., Wang, S., Zhang, X. D., Zhuang, X., Pan, L., & Liao, L. (2024) · European Review of Aging and Physical Activity · doi:10.1186/s11556-024-00359-2 · Cited by 14
“(2) Heterogeneity: To solve the heterogeneity problem, we followed previous researchers’ protocols to determine the final tally of SNPs for inclusion as genetic instruments [20].”
MethodSharifi‐Zahabi, E., Nasiri, N., Hajizadeh‐Sharafabad, F., Mohammadi, S., Shahbazi, S., & Salehi, N. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02620-8 · Cited by 10
“For example, in large-scale randomized clinical trials, the causal cardioprotective properties of HDL-C have not been demonstrated [45–48].”
Agarwal, T., Lyngdoh, T., Dudbridge, F., Chandak, G. R., Kinra, S., Prabhakaran, D., Reddy, K. S., Relton, C. L., Smith, G. D., Ebrahim, S. B. J., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228269 · Cited by 10
“for elevated triglycerides was found in a MR study as well [18].”
BackgroundLi, Q., Gao, F., Yan, B., Yang, L., Wang, W., Bai, L., Ma, X., & Yang, J. (2021) · Brain and Behavior · doi:10.1002/brb3.2183 · Cited by 10
“In recent years, MR has been widely applied to infer causal associations between various factors due to explosion in the availability of GWAS summary data (Haycock et al., 2017; Sanna et al., 2019; White et al., 2016; Yang et al., 2020).”
Georgiou, A. N., Zagkos, L., Markozannes, G., Chalitsios, C. V., Asimakopoulos, A., Xu, W., Wang, L., Mesa‐Eguiagaray, I., Zhou, X., Loizidou, E. M., et al. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.122.029040 · Cited by 10
Causal Association between Whole-Body Water Mass and Sleep Apnea: A Mendelian Randomization Study
Zhou, T., Xie, J., Wang, X., Gui, C., Wang, Y., Liang, T., Kuang, X., Liao, W., Song, L., & Zhang, X. (2022) · Annals of the American Thoracic Society · doi:10.1513/annalsats.202112-1331oc · Cited by 10
High-density lipoproteins. Part 2. Impact of disease states on functionality
Gluba-Brzózka, A., Olszewski, R., Franczyk, B., Młynarska, E., Rysz-Górzyńska, M., Rysz, J., Surma, S., Sheth, S., Banach, M., & Toth, P. P. (2025) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2025.101073 · Cited by 12
“Third, rigorous Mendelian randomization studies have failed to demonstrate a causal role for HDL particles in atherogenesis[9 – 11].”
Liu, T.-D., Sun, S., Zheng, Y.-Y., & Zhang, J. (2025) · Scientific Reports · doi:10.1038/s41598-025-21485-6 · Cited by 9
Common and rare genetic variants and risk of CHD
Swerdlow, D. I., & Humphries, S. E. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.209 · Cited by 9
Self-citationHigh Density Lipoproteins: Is There a Comeback as a Therapeutic Target?
von Eckardstein, A. (2021) · Handbook of experimental pharmacology · doi:10.1007/164_2021_536 · Cited by 9
Virgin Coconut Oil: A Dietary Intervention for Dyslipidaemia in Patients with Diabetes Mellitus
Setyawati, A., Sangkala, M. S., Malasari, S., Jafar, N., Sjattar, E. L., Syahrul, S., & Rasyid, H. (2023) · Nutrients · doi:10.3390/nu15030564 · Cited by 9
“Lipid fractions of low-density lipoprotein (LDL), high-density lipoprotein (HDL) and possibly triglyceride (TG) are causally related to CAD in people with DM [3].”
BackgroundPhenome-wide Mendelian randomization study of plasma triglyceride levels and 2600 disease traits
Park, J. K., Bafna, S., Forrest, I. S., Duffy, Á., Márquez‐Luna, C., Petrazzini, B. O., Vy, H. M. T., Jordan, D. M., Verbanck, M., Narula, J., et al. (2023) · eLife · doi:10.7554/elife.80560 · Cited by 9
Apolipoprotein M and Sphingosine-1-Phosphate: A Potentially Antidiabetic Tandem Carried by HDL
Yalçınkaya, M., & von Eckardstein, A. (2020) · Diabetes · doi:10.2337/dbi20-0005 · Cited by 9
“Mustafa Yalcinkaya and Arnold von Eckardstein Diabetes 2020;69:859–861 | https://doi.org/10.2337/dbi20-0005 The frequent finding of low HDL cholesterol in patients with type 2 diabetes (T2D) or at increased risk for T2D has been traditionally interpreted as the consequence of hypertriglyceridemia and hyperacylemia, wh…”
BackgroundInfluentialSong, W., Guan, J., He, P., Fan, S., Zhi, H., & Wang, L. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01325-4 · Cited by 9
Yang, R., Wu, S., Zhao, Z., Deng, X., Deng, Q.-Y., Wang, D., & Liu, Q. (2024) · Clinical Research in Cardiology · doi:10.1007/s00392-024-02420-7 · Cited by 8
“Large-scale observational [36], interventional [37, 38], and genetic studies [12, 13, 19] support LDL and triglycerides as being causal in the aetiology of CAD.”
Chen, S., Sun, S., Cai, M., Zhou, Z., Ma, Y., Zhou, Z., Wang, F., Liu, J., Song, W., Liu, Y., et al. (2024) · Journal of Ovarian Research · doi:10.1186/s13048-024-01486-1 · Cited by 8
“Over the past decade, the application of MR to publicly available GWAS data has seen a surge in popularity with significant results yielded [34, 35].”
BackgroundYin, L., Feng, Y., Shi, Y., Lau, A., Qiu, J., Sham, P. C., & So, H. (2024) · Nature Machine Intelligence · doi:10.1038/s42256-024-00906-7 · Cited by 14
“Two-and three-trait analyses were performed to demonstrate the utility of the proposed framework in identifying causally relevant genes for multiple traits (Supplementary Table 17).”
Metadata
- Authors
- White, J., Swerdlow, D. I., Preiss, D., Fairhurst-Hunter, Z., Keating, B. J., Asselbergs, F. W., Sattar, N., Humphries, S. E., Hingorani, A. D., & Holmes, M. V.
- Affiliations
- University College London (GB)
- Farr Institute (GB)
- University of Oxford (GB)
- Centre for Human Genetics (GB)
- Children's Hospital of Philadelphia (US)
- University Medical Center Utrecht (NL)
- University of Glasgow (GB)
- British Heart Foundation (GB)
- Corresponding author
- Holmes, Michael V.
- ORCID
- Venue
- JAMA Cardiology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-09-01
- Volume
- 1
- Issue
- 6
- Pages
- 692
- ISSN
- 2380-6583 (ISSN-L)
- PMC
- PMC5642865
- OpenAlex
- W2481252033
- Cited by
- 293
- References
- 40
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 38 · 2023: 36 · 2022: 24 · 2021: 34 · 2020: 34 · 2019: 20 · 2018: 42 · 2017: 37 · 2016: 5
- FWCI
- 38.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- JAMA Cardiology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0515-10091, ACF-2015-21-003)
- British Heart Foundation (PG 08/008, RG/10/12/28456)
- Medical Research Council (MR/K006584/1)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- LDL cholesterol, HDL cholesterol, triglycerides, coronary artery disease, type 2 diabetes, lipid fractions, statin therapy, pleiotropy, genetic instruments, multivariate Mendelian randomization, MR-Egger, causal inference, single nucleotide polymorphisms, polygenic risk score, cardiovascular risk prediction
- MeSH terms
- Coronary Artery Disease, Diabetes Mellitus, Type 2, Humans, Lipids, Cholesterol, HDL, Cholesterol, LDL, Risk Factors, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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
