title: Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans.
abstract: Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 x 10-9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans-populations that are understudied for hypertension genetic risk factors.
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.affiliation: Center for Translational Science, George Washington University and Children's National Medical Center, Washington, District of Columbia, United States of America.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Carty
authors.affiliation: Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: Division of Biostatistics, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Yun Ju
authors.initials: YJ
authors.lastname: Sung
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, 22908, United States of America.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Jeff
authors.initials: J
authors.lastname: Haessler
authors.affiliation: Brown Foundation Institute of Molecular Medicine & Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Division of Biostatistics, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Schwander
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Niha
authors.initials: N
authors.lastname: Zubair
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bien
authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.affiliation: Institute for Translational Genomics and Population Sciences and Department of Pediatrics, LABiomed at Harbor-University of California at Los Angeles Medical Center, Torrance, California, United States of America.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Suzette J
authors.initials: SJ
authors.lastname: Bielinski
authors.affiliation: Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Georg
authors.initials: G
authors.lastname: Ehret
authors.affiliation: Department of Environmental and Occupational Health Sciences, Epidemiology, and Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kaufman
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, 22908, United States of America.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.affiliation: Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Bottinger
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Division of Biostatistics, Washington University, St. Louis, Missouri, United States of America.
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
authors.affiliation: Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Paula Q
authors.initials: PQ
authors.lastname: Barrett
authors.affiliation: Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.affiliation: Department of Statistics and Biostatistics, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Buyske
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics; D040641:Quantitative Trait Loci; D062085:RNA, Long Noncoding / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D062085:RNA, Long Noncoding; C000613830:long noncoding RNA HOTTIP, human; C420132:potassium channel subfamily K member 3