Author + information
- Received July 20, 2016
- Revision received November 6, 2016
- Accepted January 3, 2017
- Published online March 20, 2017.
- Girish N. Nadkarni, MD, MPH, CPHa,
- Geneviève Galarneau, PhDa,
- Stephen B. Ellis, MSa,
- Rajiv Nadukuru, MSa,
- Jinglan Zhang, PhDa,
- Stuart A. Scott, PhDa,
- Claudia Schurmann, PhDa,
- Rongling Li, MD, PhD, MPHb,
- Laura J. Rasmussen-Torvik, PhDc,
- Abel N. Kho, MDc,
- M. Geoffrey Hayes, PhDd,
- Jennifer A. Pacheco, MSc,
- Teri A. Manolio, MD, PhDb,
- Rex L. Chisholm, PhDc,
- Dan M. Roden, MDe,
- Joshua C. Denny, MD, MSe,
- Eimear E. Kenny, PhDa and
- Erwin P. Bottinger, MDa,∗ ()
- aCharles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
- bDivision of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland
- cCenter for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- dDivision of Endocrinology, Metabolism, & Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- eDepartment of Medicine and Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee
- ↵∗Address for correspondence:
Dr. Erwin P. Bottinger, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine Mount Sinai, One Gustave L. Levy Place, Box 1003, New York, New York 10029.
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.
Objectives 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.
The BioMe health care delivery cohort at Mount Sinai was established and maintained with a generous gift from the Andrea and Charles Bronfman Philanthropies. The eMERGE Network was initiated and funded by National Human Genome Research Institute through the following grants: U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation, and Pennsylvania State University), U01HG006382 (Geisinger Clinic), U01HG006375 (Group Health Cooperative/University of Washington), U01HG006379 (Mayo Clinic), U01HG006380 (Icahn School of Medicine at Mount Sinai), U01HG006388 (Northwestern University), U01HG006378 (Vanderbilt University Medical Center), and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG004438 (CIDR) and U01HG004424 (the Broad Institute) served as Genotyping Centers. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number K23DK107908 (to Dr. Nadkarni). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Galarneau is a recipient of a Canadian Institute of Health Research postdoctoral fellowship award (MFE-140913). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Nadkarni and Galarneau contributed equally to this work. Thomas D. Giles, MD, served as the Guest Editor for this article.
- Received July 20, 2016.
- Revision received November 6, 2016.
- Accepted January 3, 2017.
- 2017 American College of Cardiology Foundation