Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans

Nora Franceschini; Cara L Carty; Yingchang Lu; Ran Tao; Yun Ju Sung; Ani Manichaikul; Jeff Haessler; Myriam Fornage; Karen Schwander; Niha Zubair; Stephanie Bien; Lucia A Hindorff; Xiuqing Guo; Suzette J Bielinski; Georg Ehret; Joel D Kaufman; Stephen S Rich; Christopher S Carlson; Erwin P Bottinger; Kari E North; D C Rao; Aravinda Chakravarti; Paula Q Barrett; Ruth J F Loos; Steven Buyske; Charles Kooperberg

doi:10.1371/journal.pone.0164132

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Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans

Journal article

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Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans

Nora Franceschini, Cara L Carty, Yingchang Lu, Ran Tao, Yun Ju Sung, Ani Manichaikul, Jeff Haessler, Myriam Fornage, Karen Schwander, Niha Zubair, …

PloS one, Vol.11(10), pp.e0164132-e0164132

2016

DOI: https://doi.org/10.1371/journal.pone.0164132

PMCID: PMC5063457

PMID: 27736895

Abstract

African Americans - genetics

Blood Pressure - genetics

Genetic Variation

Genome-Wide Association Study - methods

Hispanic Americans - genetics

Humans

Nerve Tissue Proteins - genetics

Potassium Channels, Tandem Pore Domain - genetics

Quantitative Trait Loci

RNA, Long Noncoding - genetics

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.

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Title: Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans
Creators: Nora Franceschini - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America
Cara L Carty - Center for Translational Science, George Washington University and Children's National Medical Center, Washington, District of Columbia, United States of America
Yingchang Lu - 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
Ran Tao - Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America
Yun Ju Sung - Division of Biostatistics, Washington University, St. Louis, Missouri, United States of America
Ani Manichaikul - Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, 22908, United States of America
Jeff Haessler - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
Myriam Fornage - Brown Foundation Institute of Molecular Medicine & Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America
Karen Schwander - Division of Biostatistics, Washington University, St. Louis, Missouri, United States of America
Niha Zubair - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
Stephanie Bien - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
Lucia A Hindorff - Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Xiuqing Guo - 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
Suzette J Bielinski - Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America
Georg Ehret - Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva, Switzerland
Joel D Kaufman - Department of Environmental and Occupational Health Sciences, Epidemiology, and Medicine, University of Washington, Seattle, Washington, United States of America
Stephen S Rich - Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, 22908, United States of America
Christopher S Carlson - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
Erwin P Bottinger - 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
Kari E North - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America
D C Rao - Division of Biostatistics, Washington University, St. Louis, Missouri, United States of America
Aravinda Chakravarti - Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Paula Q Barrett - Department of Pharmacology, University of Virginia, Charlottesville, Virginia, United States of America
Ruth J F Loos - 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
Steven Buyske - Department of Statistics and Biostatistics, Rutgers University, Piscataway, New Jersey, United States of America
Charles Kooperberg - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
Publication Details: PloS one, Vol.11(10), pp.e0164132-e0164132
Date published: 2016
Grant note: N01HC95169 / NHLBI NIH HHS HHSN268201100004I / NHLBI NIH HHS U01 HG004803 / NHGRI NIH HHS R21 HL123677 / NHLBI NIH HHS HHSN268201100007C / NHLBI NIH HHS U01 HG004402 / NHGRI NIH HHS R01 HL098077 / NHLBI NIH HHS P50 ES015915 / NIEHS NIH HHS HHSN268201100004C / WHI NIH HHS HHSN268201100005G / NHLBI NIH HHS R01 HL071251 / NHLBI NIH HHS HHSN268201100002C / WHI NIH HHS P30 ES010126 / NIEHS NIH HHS N01HC95163 / NHLBI NIH HHS P30 DK020541 / NIDDK NIH HHS N01HC95166 / NHLBI NIH HHS HHSN268201100003C / WHI NIH HHS HHSN268201100011C / NHLBI NIH HHS HHSN268201100011I / NHLBI NIH HHS HHSN268201100007I / NHLBI NIH HHS R01 HG006124 / NHGRI NIH HHS HHSN268201100010C / NHLBI NIH HHS UL1 RR025005 / NCRR NIH HHS U01 HG004802 / NHGRI NIH HHS HHSN268201100005C / NHLBI NIH HHS R01 HL059367 / NHLBI NIH HHS R01 HL089717 / NHLBI NIH HHS HHSN268201100046C / NHLBI NIH HHS HHSN268201100005I / NHLBI NIH HHS UL1 RR033176 / NCRR NIH HHS UL1 TR000075 / NCATS NIH HHS N01HC95168 / NHLBI NIH HHS UL1 TR000040 / NCATS NIH HHS R01 HL071258 / NHLBI NIH HHS U01 HG007376 / NHGRI NIH HHS N01HC95165 / NHLBI NIH HHS P30 DK063491 / NIDDK NIH HHS N01HC95162 / NHLBI NIH HHS HHSN271201100004C / NIA NIH HHS N01HC95161 / NHLBI NIH HHS R01 HL071250 / NHLBI NIH HHS HHSN268201100012C / NHLBI NIH HHS N01HC95164 / NHLBI NIH HHS HHSN268201100008I / NHLBI NIH HHS R01 HL071051 / NHLBI NIH HHS N01HC95167 / NHLBI NIH HHS N02HL64278 / NHLBI NIH HHS HHSN268201100003I / NHLBI NIH HHS U01 HG004798 / NHGRI NIH HHS N01HC95159 / NHLBI NIH HHS HHSN268201100006C / NHLBI NIH HHS UL1 TR001079 / NCATS NIH HHS UL1 TR000124 / NCATS NIH HHS HHSN268201100002I / NHLBI NIH HHS HHSN268201100001C / WHI NIH HHS S10 OD020069 / NIH HHS HHSN268201100008C / NHLBI NIH HHS N01HC95160 / NHLBI NIH HHS R01 HL071259 / NHLBI NIH HHS R01 HL086694 / NHLBI NIH HHS HHSN268201100001I / NHLBI NIH HHS R01 HL087641 / NHLBI NIH HHS U01 HG004790 / NHGRI NIH HHS R01 HL071205 / NHLBI NIH HHS HHSN268201100009C / NHLBI NIH HHS U01 HG004801 / NHGRI NIH HHS HHSN268201100009I / NHLBI NIH HHS
Academic Unit: Statistics (SAS)
Language: English
Resource Type: Journal article
Identifiers: 991031665565104646