Fan, Qiao and Maranville, Joseph C. and Fritsche, Lars and Sim, Xueling and Cheung, Chui Ming Gemmy and Chen, Li Jia and Gorski, Mathias and Yamashiro, Kenji and Ahn, Jeeyun and Laude, Augustinus and Dorajoo, Rajkumar and Lim, Tock Han and Teo, Yik-Ying and Blaustein, Robert O. and Yoshimura, Nagahisa and Park, Kyu-Hyung and Pang, Chi Pui and Tai, E. Shyong and Khor, Chiea Chuen and Wong, Tien Yin and Runz, Heiko and Cheng, Ching-Yu (2017) HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 46 (6). pp. 1891-1902. ISSN 0300-5771, 1464-3685
Full text not available from this repository. (Request a copy)Abstract
Dyslipidemia, particularly high-density lipoprotein cholesterol (HDL-C), has recently been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss. However, epidemiological studies have yielded conflicting results. We investigated the causal role of plasma lipid levels in AMD in multiethnic populations comprising 16 144 advanced AMD cases and 17 832 controls of European descent, together with 2219 cases and 5275 controls of Asian descent, using Mendelian randomization in three models. Model 1 is a conventional meta-analysis which does not account for pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate, inverse variance weighted regression analysis that accounts for potential unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate regression analysis that addresses pleiotropy by MR-Egger method and by adjusting for effects on other lipid traits. A 1 standard deviation (SD) higher HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95% confidence interval: 1.07-1.29) in Europeans (P = 6.88 x 10(-4)) and of 1.58 (1.24-2.00) in Asians (P = 2.92 x 10(-4)) in Model 3. The corresponding OR estimates were 1.30 (1.09-1.55) in Europeans (P = 3.18 x 10(-3)) and 1.42 (1.11-1.80) in Asians (P = 4.42 x 10(-3)) in Model 1, and 1.21 (1.11-1.31) in Europeans (P = 3.12 x 10(-5)) and 1.51 (1.20-1.91) in Asians (P = 7.61 x 10(-4)) in Model 2. Conversely, neither LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3) nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P = 0.613) were associated with AMD. We also assessed the association between lipid levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD, and found a similar trend for association of PCV with HDL-C levels. Our study shows that high levels of plasma HDL-C are causally associated with an increased risk for advanced AMD in European and Asian populations, implying that strategies reducing HDL-C levels may be useful to prevent and treat AMD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH-DENSITY-LIPOPROTEIN; POLYPOIDAL CHOROIDAL VASCULOPATHY; CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; SERUM-LIPOPROTEIN; COMMON VARIANTS; EYE; SUSCEPTIBILITY; MACULOPATHY; LOCI; HDL-cholesterol; AMD; lipids; Mendelian randomization; genetic association |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 20 Feb 2019 15:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1755 |
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