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HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization

BACKGROUND: 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. METHODS: We investigat...

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Autores principales: Fan, Qiao, Maranville, Joseph C, Fritsche, Lars, Sim, Xueling, Cheung, Chui Ming Gemmy, Chen, Li Jia, Gorski, Mathias, Yamashiro, Kenji, Ahn, Jeeyun, Laude, Augustinus, Dorajoo, Rajkumar, Lim, Tock Han, Teo, Yik-Ying, Blaustein, Robert O, Yoshimura, Nagahisa, Park, Kyu-Hyung, Pang, Chi Pui, Tai, E Shyong, Khor, Chiea Chuen, Wong, Tien Yin, Runz, Heiko, Cheng, Ching-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837540/
https://www.ncbi.nlm.nih.gov/pubmed/29025108
http://dx.doi.org/10.1093/ije/dyx189
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author Fan, Qiao
Maranville, Joseph C
Fritsche, Lars
Sim, Xueling
Cheung, Chui Ming Gemmy
Chen, Li Jia
Gorski, Mathias
Yamashiro, Kenji
Ahn, Jeeyun
Laude, Augustinus
Dorajoo, Rajkumar
Lim, Tock Han
Teo, Yik-Ying
Blaustein, Robert O
Yoshimura, Nagahisa
Park, Kyu-Hyung
Pang, Chi Pui
Tai, E Shyong
Khor, Chiea Chuen
Wong, Tien Yin
Runz, Heiko
Cheng, Ching-Yu
author_facet Fan, Qiao
Maranville, Joseph C
Fritsche, Lars
Sim, Xueling
Cheung, Chui Ming Gemmy
Chen, Li Jia
Gorski, Mathias
Yamashiro, Kenji
Ahn, Jeeyun
Laude, Augustinus
Dorajoo, Rajkumar
Lim, Tock Han
Teo, Yik-Ying
Blaustein, Robert O
Yoshimura, Nagahisa
Park, Kyu-Hyung
Pang, Chi Pui
Tai, E Shyong
Khor, Chiea Chuen
Wong, Tien Yin
Runz, Heiko
Cheng, Ching-Yu
author_sort Fan, Qiao
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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 × 10(–4)) and of 1.58 (1.24–2.00) in Asians (P = 2.92 × 10(–4)) in Model 3. The corresponding OR estimates were 1.30 (1.09–1.55) in Europeans (P = 3.18 × 10(–3)) and 1.42 (1.11—1.80) in Asians (P = 4.42 × 10(–3)) in Model 1, and 1.21 (1.11–1.31) in Europeans (P = 3.12 × 10(–5)) and 1.51 (1.20–1.91) in Asians (P = 7.61 × 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. CONCLUSIONS: 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.
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spelling pubmed-58375402018-03-09 HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization Fan, Qiao Maranville, Joseph C Fritsche, Lars Sim, Xueling Cheung, Chui Ming Gemmy Chen, Li Jia Gorski, Mathias Yamashiro, Kenji Ahn, Jeeyun Laude, Augustinus Dorajoo, Rajkumar Lim, Tock Han Teo, Yik-Ying Blaustein, Robert O Yoshimura, Nagahisa Park, Kyu-Hyung Pang, Chi Pui Tai, E Shyong Khor, Chiea Chuen Wong, Tien Yin Runz, Heiko Cheng, Ching-Yu Int J Epidemiol Vision BACKGROUND: 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. METHODS: 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. RESULTS: 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 × 10(–4)) and of 1.58 (1.24–2.00) in Asians (P = 2.92 × 10(–4)) in Model 3. The corresponding OR estimates were 1.30 (1.09–1.55) in Europeans (P = 3.18 × 10(–3)) and 1.42 (1.11—1.80) in Asians (P = 4.42 × 10(–3)) in Model 1, and 1.21 (1.11–1.31) in Europeans (P = 3.12 × 10(–5)) and 1.51 (1.20–1.91) in Asians (P = 7.61 × 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. CONCLUSIONS: 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. Oxford University Press 2017-12 2017-09-12 /pmc/articles/PMC5837540/ /pubmed/29025108 http://dx.doi.org/10.1093/ije/dyx189 Text en © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Vision
Fan, Qiao
Maranville, Joseph C
Fritsche, Lars
Sim, Xueling
Cheung, Chui Ming Gemmy
Chen, Li Jia
Gorski, Mathias
Yamashiro, Kenji
Ahn, Jeeyun
Laude, Augustinus
Dorajoo, Rajkumar
Lim, Tock Han
Teo, Yik-Ying
Blaustein, Robert O
Yoshimura, Nagahisa
Park, Kyu-Hyung
Pang, Chi Pui
Tai, E Shyong
Khor, Chiea Chuen
Wong, Tien Yin
Runz, Heiko
Cheng, Ching-Yu
HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization
title HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization
title_full HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization
title_fullStr HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization
title_full_unstemmed HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization
title_short HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization
title_sort hdl-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using mendelian randomization
topic Vision
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837540/
https://www.ncbi.nlm.nih.gov/pubmed/29025108
http://dx.doi.org/10.1093/ije/dyx189
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