Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study
Authors: 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 , Penman Alan , Mitchell Paul , Liew Gerald , Smith Albert V. , Gudnason Vilmundur , Tan Gavin , Klein Barbara E.K. , Kuo Jane , Li Xiaohui , Christiansen Mark W. , Psaty Bruce M. , Sandow Kevin , 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 ,   Asian Genetic Epidemiology Network Consortium, Spracklen Cassandra N. , Chen Peng , Kim Young Jin , Wang Xu , Cai Hui , Li Shengxu , Long Jirong , Wu Ying , Wang Ya-Xing , Takeuchi Fumihiko , Wu Jer-Yuarn , Jung Keum-Ji , Hu Cheng , Akiyama Koichi , Zhang Yonghong , Moon Sanghoon , Johnson Todd A. , Li Huaixing , Dorajoo Rajkumar , He Meian , Cannon Maren E. , Roman Tamara S. , Salfati Elias , Lin Keng-Hung , Sheu Wayne H.H. , Absher Devin , Adair Linda S. , Assimes Themistocles L. , Aung Tin , Cai Qiuyin , Chang Li-Ching , Chen Chien-Hsiun , Chien Li-Hsin , Chuang Lee-Ming , Chuang Shu-Chun , Du Shufa , Fann Cathy S.J. , Feranil Alan B. , Friedlander Yechiel , Gordon-Larsen Penny , Gu Dongfeng , Gui Lixuan , Guo Zhirong , Heng Chew-Kiat , Hixson James , Hou Xuhong , Hsiung Chao Agnes , Hu Yao , Hwang Mi Yeong , Hwu Chii-Min , Isono Masato , Juang Jyh-Ming Jimmy , Khor Chiea-Chuen , Kim Yun Kyoung , Koh Woon-Puay , Kubo Michiaki , Lee I-Te , Lee Sun-Ju , Liang Kae-Woei , Lim Blanche , Lim Sing-Hui , Liu Jianjun , Nabika Toru , Pan Wen-Harn , Peng Hao , Quertermous Thomas , Sabanayagam Charumathi , Shi Jinxiu , Sun Liang , Tan Pok Chien , Tan Shu-Pei , Taylor Kent D. , Teo Yik-Ying , Toh Sue-Anne , Tsunoda Tatsuhiko , van Dam Rob M. , Wang Aili , Wang Feijie , Wang Jie , Wei Wen Bin , Xiang Yong-Bing , Yao Jie , Yuan Jian-Min , Zhang Rong , Zhao Wanting , Rich Stephen S. , Wang Tzung-Dau , Wu Tangchun , Lin Xu , Han Bok-Ghee , Tanaka Toshihiro , Cho Yoon Shin , Katsuya Tomohiro , Jia Weiping , Jee Sun-Ha , Chen Yuan-Tsong , Kato Norihiro , Jonas Jost B. , Shu Xiao-Ou , He Jiang , Zheng Wei , Huang Wei , Kim Bong-Jo , Tai E-Shyong , Mohlke Karen L. , Sim Xueling 
Published: September 2017

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.