Association of APOL1 Risk Alleles With Cardiovascular Disease in Blacks in the Million Veteran Program.
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Bick Alexander G, Akwo Elvis, Robinson-Cohen Cassianne, Lee Kyung, Lynch Julie, Assimes Themistocles L, DuVall Scott, Edwards Todd, Fang Huaying, Freiberg S Matthew, Giri Ayush, Huffman Jennifer E, Huang Jie, Hull Leland, Kember Rachel L, Klarin Derek, Lee Jennifer S, Levin Michael, Miller Donald R, Natarajan Pradeep, Saleheen Danish, Shao Qing, Sun Yan V, Tang Hua, Wilson Otis, Chang Kyong-Mi, Cho Kelly, Concato John, Gaziano J Michael, Kathiresan Sekar, O'Donnell Christopher J, Rader Daniel J, Tsao Philip S, Wilson Peter W, Hung Adriana M, Damrauer Scott M, VA Million Veteran Program
Аннотация
METHODS: We performed a time-to-event analysis of retrospective electronic health record data using Cox proportional hazard and competing-risks Fine and Gray subdistribution hazard models. The primary exposure was APOL1 risk allele status. The primary outcome was incident coronary artery disease among individuals without chronic kidney disease during the 12.5-year follow-up period. We separately analyzed the cross-sectional association of APOL1 risk allele status with lipid traits and 115 cardiovascular diseases using phenome-wide association.
RESULTS: Among 30 903 black Million Veteran Program participants, 3941 (13%) carried the 2 APOL1 risk allele high-risk genotype. Individuals with normal kidney function at baseline with 2 risk alleles had slightly higher risk of developing coronary artery disease compared with those with no risk alleles (hazard ratio, 1.11 [95% CI, 1.01-1.21]; P=0.039). Similarly, modest associations were identified with incident stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36; P=0.007) and peripheral artery disease (hazard ratio, 1.15 [95% CI, 1.01-1.29l; P=0.031). When both cardiovascular and renal outcomes were modeled, APOL1 was strongly associated with incident renal disease, whereas no significant association with the CVD end points could be detected. Cardiovascular phenome-wide association analyses did not identify additional significant associations with CVD subsets.
CONCLUSIONS: APOL1 risk variants display a modest association with CVD, and this association is likely mediated by the known APOL1 association with chronic kidney disease.