Title | Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Sobrin, L, Chong, YHe, Fan, Q, Gan, A, Stanwyck, LK, Kaidonis, G, Craig, JE, 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, Mitchell, P, Liew, G, Smith, AV, Gudnason, V, Tan, G, Klein, BEK, Kuo, J, Li, X, Christiansen, MW, Psaty, BM, Sandow, K, Jensen, RA, Klein, R, Cotch, MFrances, Wang, JJin, Jia, Y, Chen, CJ, Chen, Y-DI, Rotter, JI, Tsai, F-J, Hanis, CL, Burdon, KP, Wong, TYin, Cheng, C-Y |
Corporate/Institutional Authors | Asian Genetic Epidemiology Network Consortium |
Journal | Diabetes |
Volume | 66 |
Issue | 12 |
Pagination | 3130-3141 |
Date Published | 2017 12 |
ISSN | 1939-327X |
Keywords | Aged, Diabetic Retinopathy, Female, Genome-Wide Association Study, Humans, Lipids, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk |
Abstract | <p>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.</p> |
DOI | 10.2337/db17-0398 |
Alternate Journal | Diabetes |
PubMed ID | 28951389 |
PubMed Central ID | PMC5697951 |
Grant List | HHSN268201500003C / HL / NHLBI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States K12 EY016335 / EY / NEI NIH HHS / United States HHSN268201300048C / HL / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N02HL64278 / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268201300049C / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States HHSN268201300047C / HL / NHLBI NIH HHS / United States HHSN268201300050C / HL / NHLBI NIH HHS / United States ZIA AG007380 / AG / NIA NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States / / Wellcome Trust / United Kingdom HHSN268201300046C / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States R01 EY022302 / EY / NEI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States ZIA EY000401 / EY / NEI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States |