Priyanka Nandakumar1, Dongwon Lee, Melissa A Richard, Fasil Tekola-Ayele, Bamidele O Tayo, Erin Ware, Yun J Sung, Babatunde Salako, Adesola Ogunniyi, C Charles Gu, Megan L Grove, Myriam Fornage, Sharon Kardia, Charles Rotimi, Richard S Cooper, Alanna C Morrison, Georg Ehret, Aravinda Chakravarti. 1. 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.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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: S L Ataman; R Cooper; C Rotimi; D McGee; B Osotimehin; S Kadiri; S Kingue; W Muna; H Fraser; T Forrester; R Wilks Journal: J Clin Epidemiol Date: 1996-08 Impact factor: 6.437
Authors: Christopher J Staples; Katie N Myers; Ryan D D Beveridge; Abhijit A Patil; Anna E Howard; Giancarlo Barone; Alvin J X Lee; Charles Swanton; Michael Howell; Sarah Maslen; J Mark Skehel; Simon J Boulton; Spencer J Collis Journal: J Cell Sci Date: 2014-05-09 Impact factor: 5.285
Authors: Jeannette Simino; Gang Shi; Joshua C Bis; Daniel I Chasman; Georg B Ehret; Xiangjun Gu; Xiuqing Guo; Shih-Jen Hwang; Eric Sijbrands; Albert V Smith; Germaine C Verwoert; Jennifer L Bragg-Gresham; Gemma Cadby; Peng Chen; Ching-Yu Cheng; Tanguy Corre; Rudolf A de Boer; Anuj Goel; Toby Johnson; Chiea-Chuen Khor; Carla Lluís-Ganella; Jian'an Luan; Leo-Pekka Lyytikäinen; Ilja M Nolte; Xueling Sim; Siim Sõber; Peter J van der Most; Niek Verweij; Jing Hua Zhao; Najaf Amin; Eric Boerwinkle; Claude Bouchard; Abbas Dehghan; Gudny Eiriksdottir; Roberto Elosua; Oscar H Franco; Christian Gieger; Tamara B Harris; Serge Hercberg; Albert Hofman; Alan L James; Andrew D Johnson; Mika Kähönen; Kay-Tee Khaw; Zoltan Kutalik; Martin G Larson; Lenore J Launer; Guo Li; Jianjun Liu; Kiang Liu; Alanna C Morrison; Gerjan Navis; Rick Twee-Hee Ong; George J Papanicolau; Brenda W Penninx; Bruce M Psaty; Leslie J Raffel; Olli T Raitakari; Kenneth Rice; Fernando Rivadeneira; Lynda M Rose; Serena Sanna; Robert A Scott; David S Siscovick; Ronald P Stolk; Andre G Uitterlinden; Dhananjay Vaidya; Melanie M van der Klauw; Ramachandran S Vasan; Eranga Nishanthie Vithana; Uwe Völker; Henry Völzke; Hugh Watkins; Terri L Young; Tin Aung; Murielle Bochud; Martin Farrall; Catharina A Hartman; Maris Laan; Edward G Lakatta; Terho Lehtimäki; Ruth J F Loos; Gavin Lucas; Pierre Meneton; Lyle J Palmer; Rainer Rettig; Harold Snieder; E Shyong Tai; Yik-Ying Teo; Pim van der Harst; Nicholas J Wareham; Cisca Wijmenga; Tien Yin Wong; Myriam Fornage; Vilmundur Gudnason; Daniel Levy; Walter Palmas; Paul M Ridker; Jerome I Rotter; Cornelia M van Duijn; Jacqueline C M Witteman; Aravinda Chakravarti; Dabeeru C Rao Journal: Am J Hum Genet Date: 2014-06-19 Impact factor: 11.025
Authors: Charles N Rotimi; Amy R Bentley; Ayo P Doumatey; Guanjie Chen; Daniel Shriner; Adebowale Adeyemo Journal: Hum Mol Genet Date: 2017-10-01 Impact factor: 6.150