학술논문

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study
Document Type
article
Author
Sobrin, LuciaChong, Yong HeFan, QiaoGan, AlfredStanwyck, Lynn KKaidonis, GeorgiaCraig, Jamie EKim, JihyeLiao, Wen-LingHuang, Yu-ChuenLee, Wen-JaneHung, Yi-JenGuo, XiuqingHai, YangIpp, EliPollack, SamuelaHancock, HeatherPrice, AlkesPenman, AlanMitchell, PaulLiew, GeraldSmith, Albert VGudnason, VilmundurTan, GavinKlein, Barbara EKKuo, JaneLi, XiaohuiChristiansen, Mark WPsaty, Bruce MSandow, KevinJensen, Richard AKlein, RonaldCotch, Mary FrancesWang, Jie JinJia, YuchengChen, Ching JChen, Yii-Der IdaRotter, Jerome ITsai, Fuu-JenHanis, Craig LBurdon, Kathryn PWong, Tien YinCheng, Ching-YuSpracklen, Cassandra NChen, PengKim, Young JinWang, XuCai, HuiLi, ShengxuLong, JirongWu, YingWang, Ya-XingTakeuchi, FumihikoWu, Jer-YuarnJung, Keum-JiHu, ChengAkiyama, KoichiZhang, YonghongMoon, SanghoonJohnson, Todd ALi, HuaixingDorajoo, RajkumarHe, MeianCannon, Maren ERoman, Tamara SSalfati, EliasLin, Keng-HungSheu, Wayne HHAbsher, DevinAdair, Linda SAssimes, Themistocles LAung, TinCai, QiuyinChang, Li-ChingChen, Chien-HsiunChien, Li-HsinChuang, Lee-MingChuang, Shu-ChunDu, ShufaFann, Cathy SJFeranil, Alan BFriedlander, YechielGordon-Larsen, PennyGu, DongfengGui, LixuanGuo, ZhirongHeng, Chew-KiatHixson, JamesHou, XuhongHsiung, Chao AgnesHu, YaoHwang, Mi YeongHwu, Chii-MinIsono, MasatoJuang, Jyh-Ming JimmyKhor, Chiea-ChuenKim, Yun KyoungKoh, Woon-PuayKubo, MichiakiLee, I-Te
Source
Diabetes. 66(12)
Subject
Biomedical and Clinical Sciences
Cancer
Prevention
Eye Disease and Disorders of Vision
2.1 Biological and endogenous factors
Aetiology
Metabolic and endocrine
Aged
Diabetic Retinopathy
Female
Genome-Wide Association Study
Humans
Lipids
Male
Mendelian Randomization Analysis
Middle Aged
Polymorphism
Single Nucleotide
Risk
Asian Genetic Epidemiology Network Consortium
Medical and Health Sciences
Endocrinology & Metabolism
Biomedical and clinical sciences
Language
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.