Journal
DIABETES
Volume 66, Issue 12, Pages 3130-3141Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db17-0398
Keywords
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Categories
Funding
- Research to Prevent Blindness, Inc.
- National Eye Institute [EY16335, EY22302, ZIAEY00401, N01-AG-1-2100]
- Massachusetts Lions Eye Research Fund
- Alcon Research Institute
- American Diabetes Association [111-CT-51]
- Harvard Catalyst
- U.S. National Institutes of Health (NIH) through National Institute on Aging [ZIAAG007380]
- Hjartavernd (the Icelandic Heart Association)
- Althingi (Icelandic Parliament)
- University of Iceland Research Fund
- National Health and Medical Research Council of Australia (NHMRC) [595918]
- Ophthalmic Research Institute of Australia
- NHMRC
- NHMRC, Canberra, Australia [974159, 211069, 302068, 529923, 512423, 475604, 529912]
- Wellcome Trust as part of Wellcome Trust Case Control Consortium 2 [085475/B/08/Z, 085475/08/Z]
- NIH National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC75150, U01HL080295, U01HL130114]
- CHARGE infrastructure grant [HL105756]
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging [R01AG023629]
- Academia Sinica, Taiwan
- Jackson State University [HHSN268201300049C, HHSN268201300050C]
- Tougaloo College [HHSN268201300048C]
- University of Mississippi Medical Center [HHSN268201300046C, HHSN268201300047C]
- NHLBI
- National Institute on Minority Health and Health Disparities
- NHLBI [HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001881, DK063491, N02-HL-64278]
- National Medical Research Council, Singapore [0796/2003, 1176/2008, 1149/2008, STaR/0003/2008, 1249/2010, CG/SERI/2010, CIRG/1371/2013, CIRG/1417/2015]
- Biomedical Research Council, Singapore [08/1/35/19/550, 09/1/35/19/616]
- National Medical Research Council [CSA/033/2012]
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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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