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Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk.

TitleRare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk.
Publication TypeJournal Article
Year of Publication2016
AuthorsYu B, Pulit SL, Hwang S-J, Brody JA, Amin N, Auer PL, Bis JC, Boerwinkle E, Burke GL, Chakravarti A, Correa A, Dreisbach AW, Franco OH, Ehret GB, Franceschini N, Hofman A, Lin D-Y, Metcalf GA, Musani SK, Muzny D, Palmas W, Raffel L, Reiner A, Rice K, Rotter JI, Veeraraghavan N, Fox E, Guo X, North KE, Gibbs RA, van Duijn CM, Psaty BM, Levy D, Newton-Cheh C
Secondary AuthorsMorrison AC
Corporate AuthorsCHARGE Consortium and the National Heart, Lung, and Blood Institute GO ESP*
JournalCirc Cardiovasc Genet
Volume9
Issue1
Pagination64-70
Date Published2016 Feb
ISSN1942-3268
KeywordsAfrican Continental Ancestry Group, Alleles, Blood Pressure, Chloride Channels, European Continental Ancestry Group, Exome, Female, Gene Frequency, Humans, Hypertension, Male, Risk Factors
Abstract

BACKGROUND: Rare genetic variants influence blood pressure (BP).

METHODS AND RESULTS: Whole-exome sequencing was performed on DNA samples from 17 956 individuals of European ancestry and African ancestry (14 497, first-stage discovery and 3459, second-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Tests of ≈170 000 common variants (minor allele frequency, ≥1%; statistical significance, P≤2.9×10(-7)) and gene-based tests of rare variants (minor allele frequency,

CONCLUSIONS: These findings implicate the effect of rare coding variants in CLCN6 in BP variation and offer new insights into BP regulation.

DOI10.1161/CIRCGENETICS.115.001215
Alternate JournalCirc Cardiovasc Genet
PubMed ID26658788
PubMed Central IDPMC4771070
Grant ListR01 HL059367 / HL / NHLBI NIH HHS / United States
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R01 CA082659 / CA / NCI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201000010C / HL / NHLBI NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
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P30 ES010126 / ES / NIEHS NIH HHS / United States
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