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

TitleVariant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans.
Publication TypePublication
Year2016
AuthorsFranceschini N, Carty CL, Lu Y, Tao R, Sung YJu, Manichaikul A, Haessler J, Fornage M, Schwander K, Zubair N, Bien S, Hindorff LA, Guo X, Bielinski SJ, Ehret G, Kaufman JD, Rich SS, Carlson CS, Bottinger EP, North KE, Rao DC, Chakravarti A, Barrett PQ, Loos RJF, Buyske S, Kooperberg C
JournalPLoS One
Volume11
Issue10
Paginatione0164132
Date Published2016
ISSN1932-6203
KeywordsAfrican Americans, blood pressure, Genetic Variation, genome-wide association study, Hispanic Americans, Humans, Nerve Tissue Proteins, Potassium Channels, Tandem Pore Domain, Quantitative Trait Loci, RNA, Long Noncoding
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.

DOI10.1371/journal.pone.0164132
Alternate JournalPLoS One
PubMed ID27736895
PubMed Central IDPMC5063457
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 HL071251 / HL / NHLBI NIH HHS / United States
R01 HL071259 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
UL1 TR000075 / TR / NCATS NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
R01 HL071250 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
U01 HG007376 / HG / NHGRI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
R01 HL098077 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
P50 ES015915 / ES / NIEHS NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL071051 / HL / NHLBI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
R01 HL089717 / HL / NHLBI NIH HHS / United States
R01 HG006124 / HG / NHGRI NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
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HHSN268201100009C / HL / NHLBI NIH HHS / United States
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S10 OD020069 / OD / NIH HHS / United States
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UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201100003I / HL / NHLBI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 HL071258 / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
MS#: 
0172
ECI: 
Yes
Manuscript Status: 
Published