Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration
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Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration. / Nordestgaard, Liv Tybjærg; Christoffersen, Mette; Afzal, Shoaib; Nordestgaard, Børge Grønne; Tybjærg-Hansen, Anne; Frikke-Schmidt, Ruth.
In: European Journal of Epidemiology, Vol. 38, No. 9, 2023, p. 985-994.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration
AU - Nordestgaard, Liv Tybjærg
AU - Christoffersen, Mette
AU - Afzal, Shoaib
AU - Nordestgaard, Børge Grønne
AU - Tybjærg-Hansen, Anne
AU - Frikke-Schmidt, Ruth
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - ATP-binding cassette transporter A1
KW - Blindness
KW - Cholesterol
KW - Drusen
KW - Genetics
KW - High-density lipoprotein
U2 - 10.1007/s10654-023-01021-4
DO - 10.1007/s10654-023-01021-4
M3 - Journal article
C2 - 37335386
AN - SCOPUS:85162255927
VL - 38
SP - 985
EP - 994
JO - European Journal of Epidemiology
JF - European Journal of Epidemiology
SN - 0393-2990
IS - 9
ER -
ID: 367088690