Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration

Liv Tybjærg Nordestgaard, Mette Christoffersen, Shoaib Afzal, Børge Grønne Nordestgaard, Anne Tybjærg-Hansen, Ruth Frikke-Schmidt*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Genetic variants in ABCA1 are associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are observationally and genetically associated with higher risk of age-related macular degeneration (AMD). However, whether amino acid-changing genetic variants in ABCA1 associated with high HDL cholesterol concentrations confer a higher risk of AMD in the general population is currently unknown. We tested this hypothesis. The study included 80,972 individuals (1,370 AMD cases) from the Copenhagen General Population Study (CGPS) and 9,584 individuals (142 AMD cases) from the Copenhagen City Heart Study (CCHS) with 10 to 18 years of follow-up. We created an HDL cholesterol weighted allele score based on amino acid-changing ABCA1 variants with a minor allele frequency above 0.001 and divided it into tertiles. The study included 55% women. Mean age was 58 years. The ABCA1 allele score for the third versus the first tertile was associated with HRs (95% confidence intervals (CIs)) of 1.30 (1.14–1.49) for all-cause AMD, 1.26 (1.06–1.50) for nonneovascular AMD, and 1.31 (1.12–1.53) for neovascular AMD in a multivariable adjusted model. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, nonneovascular AMD, and neovascular AMD in an age- and sex adjusted model and in a multivariable adjusted model. In conclusion, amino acid-changing genetic variants in ABCA1 associated with higher HDL cholesterol concentrations were also associated with higher risk of AMD, suggesting a role for ABCA1 in AMD pathogenesis.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Epidemiology
Vol/bind38
Udgave nummer9
Sider (fra-til)985-994
Antal sider10
ISSN0393-2990
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We are indebted to staff and participants of the Copenhagen General Population Study and the Copenhagen City Heart Study for their important contributions to our study.

Funding Information:
Open access funding provided by Royal Library, Copenhagen University Library. Funded by the Research Council at Rigshospitalet, the Danish Heart Foundation, the Lundbeck Foundation, and the Leducq Foundation. The sponsors or funding organizations had no role in the design or conduct of this research.

Publisher Copyright:
© 2023, The Author(s).

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