TY - JOUR
T1 - Association of APOL1 Risk Alleles with Cardiovascular Disease in Blacks in the Million Veteran Program
AU - Bick, Alexander G.
AU - Akwo, Elvis
AU - Robinson-Cohen, Cassianne
AU - Lee, Kyung
AU - Lynch, Julie
AU - Assimes, Themistocles L.
AU - Duvall, Scott
AU - Edwards, Todd
AU - Fang, Huaying
AU - Freiberg, S. Matthew
AU - Giri, Ayush
AU - Huffman, Jennifer E.
AU - Huang, Jie
AU - Hull, Leland
AU - Kember, Rachel L.
AU - Klarin, Derek
AU - Lee, Jennifer S.
AU - Levin, Michael
AU - Miller, Donald R.
AU - Natarajan, Pradeep
AU - Saleheen, Danish
AU - Shao, Qing
AU - Sun, Yan V.
AU - Tang, Hua
AU - Wilson, Otis
AU - Chang, Kyong Mi
AU - Cho, Kelly
AU - Concato, John
AU - Gaziano, J. Michael
AU - Kathiresan, Sekar
AU - O'Donnell, Christopher J.
AU - Rader, Daniel J.
AU - Tsao, Philip S.
AU - Wilson, Peter W.
AU - Hung, Adriana M.
AU - Damrauer, Scott M.
N1 - Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/9/17
Y1 - 2019/9/17
N2 - Background: Approximately 13% of black individuals carry 2 copies of the apolipoprotein L1 (APOL1) risk alleles G1 or G2, which are associated with 1.5- to 2.5-fold increased risk of chronic kidney disease. There have been conflicting reports as to whether an association exists between APOL1 risk alleles and cardiovascular disease (CVD) that is independent of the effects of APOL1 on kidney disease. We sought to test the association of APOL1 G1/G2 alleles with coronary artery disease, peripheral artery disease, and stroke among black individuals in the Million Veteran Program. 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.
AB - Background: Approximately 13% of black individuals carry 2 copies of the apolipoprotein L1 (APOL1) risk alleles G1 or G2, which are associated with 1.5- to 2.5-fold increased risk of chronic kidney disease. There have been conflicting reports as to whether an association exists between APOL1 risk alleles and cardiovascular disease (CVD) that is independent of the effects of APOL1 on kidney disease. We sought to test the association of APOL1 G1/G2 alleles with coronary artery disease, peripheral artery disease, and stroke among black individuals in the Million Veteran Program. 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.
KW - apolipoprotein L1
KW - cardiovascular diseases
KW - genetics
KW - renal insufficiency, chronic
UR - https://www.scopus.com/pages/publications/85072266475
U2 - 10.1161/CIRCULATIONAHA.118.036589
DO - 10.1161/CIRCULATIONAHA.118.036589
M3 - Article
C2 - 31337231
AN - SCOPUS:85072266475
SN - 0009-7322
VL - 140
SP - 1031
EP - 1040
JO - Circulation
JF - Circulation
IS - 12
ER -