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

Lucia Sobrin, Yong He Chong, Qiao Fan, Alfred Gan, Lynn Stanwyck, Georgia Kaidonis, Jamie Craig, Jihye Kim, Wen-Ling Liao, Yu-Chen Huang, Wen-Jane Lee, Yi-Jen Hung, Xiuqing Guo, Yang Hai, Eli Ipp, Samuela Pollack, Heather Hancock, Aikes Price, Alan Penman, Paul MitchellGerald Liew, Albert Smith, Vilmundur Gudnason, Gavin Tan, Barbara Klein, Jane Kuo, Xiaohui Li, Mark Christiansen, Bruce Psaty, Kevin Sandow, Richard Jensen, Ronald Klein, Mary Cotch, Jie Jin Wang, Yucheng Jia, Ching Chen, Yii-Der Chen, Jerome Rotter, Fuu-Jen Tsai, Craig Hanis, Kathryn Burdon, Tien Wong, Ching-Yu Cheng

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)3130-3141
    Number of pages12
    JournalDiabetes
    Volume66
    Issue number12
    DOIs
    Publication statusPublished - 2017

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    Sobrin, L., Chong, Y. H., Fan, Q., Gan, A., Stanwyck, L., Kaidonis, G., Craig, J., Kim, J., Liao, W-L., Huang, Y-C., Lee, W-J., Hung, Y-J., Guo, X., Hai, Y., Ipp, E., Pollack, S., Hancock, H., Price, A., Penman, A., ... Cheng, C-Y. (2017). Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study. Diabetes, 66(12), 3130-3141. https://doi.org/10.2337/db17-0398