title: Rare coding variants associated with blood pressure variation in 15 914 individuals of African ancestry.
abstract: Hypertension is a major risk factor for all cardiovascular diseases, especially among African Americans. This study focuses on identifying specific blood pressure (BP) genes using 15 914 individuals of African ancestry from eight cohorts (Africa America Diabetes Mellitus, Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in young Adults, Genetics Network, Genetic Epidemiology Network of Arteriopathy, Howard University Family Study, Hypertension Genetic Epidemiology Network, and Loyola University Chicago Cohort) to further genetic findings in this population which has generally been underrepresented in BP studies.
  
  
  
  We genotyped and performed various single variant and gene-based exome-wide analyses on 15 914 individuals on the Illumina HumanExome Beadchip v1.0 or v1.1 to test association with SBP and DBP long-term average residuals that were adjusted for age, age-squared, sex, and BMI.
  
  
  
  We identified rare variants affecting SBP and DBP in 10 genes: AFF1, GAPDHS, SLC28A3, COL6A1, CRYBA2, KRBA1, SEL1L3, YOD1, CCDC13, and QSOX1. Prior experimental evidence for six of these 10 candidate genes supports their involvement in cardiovascular mechanisms, corroborating their potential roles in BP regulation.
  
  
  
  Although our results require replication or validation due to their low numbers of carriers, and an ethnicity-specific genotyping array may be more informative, this study, which has identified several candidate genes in this population most susceptible to hypertension, presents one of the largest African-ancestry BP studies to date and the largest including analysis of rare variants.
authors.affiliation: aMcKusick-Nathans Institute of Genetic Medicine bPredoctoral Training Program in Human Genetics and Molecular Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland cBrown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas dCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland eDepartment of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois fDepartment of Epidemiology gInstitute for Social Research, University of Michigan, Ann Arbor, Michigan hDivision of Biostatistics, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA iDepartment of Medicine, University of Ibadan, Ibadan, Nigeria jHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA kDepartment of Specialties of Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Nandakumar
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Richard
authors.forename: Fasil
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authors.lastname: Tekola-Ayele
authors.forename: Bamidele O
authors.initials: BO
authors.lastname: Tayo
authors.forename: Erin
authors.initials: E
authors.lastname: Ware
authors.forename: Yun J
authors.initials: YJ
authors.lastname: Sung
authors.forename: Babatunde
authors.initials: B
authors.lastname: Salako
authors.forename: Adesola
authors.initials: A
authors.lastname: Ogunniyi
authors.forename: C Charles
authors.initials: CC
authors.lastname: Gu
authors.forename: Megan L
authors.initials: ML
authors.lastname: Grove
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Sharon
authors.initials: S
authors.lastname: Kardia
authors.forename: Charles
authors.initials: C
authors.lastname: Rotimi
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Morrison
authors.forename: Georg
authors.initials: G
authors.lastname: Ehret
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
mesh_terms: D044383:Black People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics; D015331:Cohort Studies; D059472:Exome; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D012307:Risk Factors; D001741:Black or African American