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Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele.

TitleGenome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele.
Publication TypeJournal Article
Year of Publication2011
AuthorsTin A, Woodward OM, Kao W H L, Liu C-T, Lu X, Nalls MA, Shriner D, Semmo M, Akylbekova EL, Wyatt SB, Hwang S-J, Yang Q, Zonderman AB, Adeyemo AA, Palmer C, Meng Y, Reilly M, Shlipak MG, Siscovick D, Evans MK, Rotimi CN, Flessner MF, Köttgen M, L Cupples A, Fox CS, Köttgen A
Corporate AuthorsCARe and CHARGE Consortia
JournalHum Mol Genet
Volume20
Issue20
Pagination4056-68
Date Published2011 Oct 15
ISSN1460-2083
KeywordsAdult, African Americans, Aged, Animals, CHO Cells, Cricetinae, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Gout, Humans, Loss of Heterozygosity, Male, Middle Aged, Organic Anion Transporters, Organic Cation Transport Proteins, Polymorphism, Single Nucleotide, Uric Acid, Young Adult
Abstract

Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P

DOI10.1093/hmg/ddr307
Alternate JournalHum Mol Genet
PubMed ID21768215
PubMed Central IDPMC3177647
Grant ListN01-HB-72992 / HB / NHLBI NIH HHS / United States
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Z01-AG000513 / AG / NIA NIH HHS / United States
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S06GM008016-380111 / GM / NIGMS NIH HHS / United States
U01 HL053934 / HL / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
S06GM008016-320107 / GM / NIGMS NIH HHS / United States
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N01-HB-97064 / HB / NHLBI NIH HHS / United States
R01HL092577-01A1 / HL / NHLBI NIH HHS / United States
Z01HG200362 / HG / NHGRI NIH HHS / United States
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