Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans.
BACKGROUND
African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs.


OBJECTIVE
This study assessed the APOL1 risk alleles' association with blood pressure traits in AAs.


METHODS
The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles' association with blood pressure-related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate.


RESULTS
There were 14% to 16% of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [pcom] = 1.9 × 10-5). APOL1 risk alleles were associated with overall SBP (pcom= 7.0 × 10-8) and diastolic blood pressure (pcom= 2.8 × 10-4). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (pcom= 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range.


CONCLUSIONS
APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Girish N
GN
Nadkarni
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Geneviève
G
Galarneau
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Stephen B
SB
Ellis
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Rajiv
R
Nadukuru
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Jinglan
J
Zhang
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Stuart A
SA
Scott
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Claudia
C
Schurmann
Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland.
Rongling
R
Li
Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Laura J
LJ
Rasmussen-Torvik
Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Abel N
AN
Kho
Division of Endocrinology, Metabolism, & Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
M Geoffrey
MG
Hayes
Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Jennifer A
JA
Pacheco
Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland.
Teri A
TA
Manolio
Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Rex L
RL
Chisholm
Department of Medicine and Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville Tennessee.
Dan M
DM
Roden
Department of Medicine and Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville Tennessee.
Joshua C
JC
Denny
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Eimear E
EE
Kenny
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: erwin.bottinger@mssm.edu.
Erwin P
EP
Bottinger
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
APOL1; allele; estimated glomerular filtration rate; genetic association studies; kidney disease