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Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study


Sobrin, Lucia; Chong, Yong He; Fan, Qiao; Gan, Alfred; Stanwyck, Lynn K.; Kaidonis, Georgia; Craig, Jamie E.; Kim, Jihye; Liao, Wen-Ling; & Huang, Yu-Chuen, et al. (2017). Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study. Diabetes, 66(12), 3130-3141. PMCID: PMC5697951


Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.


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Journal Article

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Sobrin, Lucia
Chong, Yong He
Fan, Qiao
Gan, Alfred
Stanwyck, Lynn K.
Kaidonis, Georgia
Craig, Jamie E.
Kim, Jihye
Liao, Wen-Ling
Huang, Yu-Chuen
Lee, Wen-Jane
Hung, Yi-Jen
Guo, Xiuqing
Hai, Yang
Ipp, Eli
Pollack, Samuela
Hancock, Heather
Price, Alkes L.
Penman, Alan D.
Mitchell, Paul
Liew, Gerald
Smith, Albert V.
Gudnason, Vilmundur G.
Tan, Gavin
Klein, Barbara E. K.
Kuo, Jane Z.
Li, Xiaohui
Christiansen, Mark W.
Psaty, Bruce M.
Sandow, Kevin
Asian Genetic Epidemiology Network Consortium,
Jensen, Richard A.
Klein, Ronald
Cotch, Mary Frances
Wang, Jie Jin
Jia, Yucheng
Chen, Ching J.
Chen, Yii-Der Ida
Rotter, Jerome I.
Tsai, Fuu-Jen
Hanis, Craig L.
Burdon, Kathryn P.
Wong, Tien Yin
Cheng, Ching-Yu
Gordon-Larsen, Penny,