Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.

TitleGenome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.
Publication TypeJournal Article
Year of Publication2009
AuthorsChambers JC, Zhang W, Li Y, Sehmi J, Wass MN, Zabaneh D, Hoggart C, Bayele H, McCarthy MI, Peltonen L, Freimer NB, Srai SK, Maxwell PH, Sternberg MJE, Ruokonen A, Abecasis G, Jarvelin M-R, Scott J, Elliott P, Kooner JS
JournalNat Genet
Volume41
Issue11
Pagination1170-2
Date Published11/2009
ISSN1546-1718
KeywordsBinding Sites, Biocatalysis, European Continental Ancestry Group, Genome-Wide Association Study, Hemoglobins, Humans, Membrane Proteins, Models, Molecular, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Serine Endopeptidases
Abstract

We carried out a genome-wide association study of hemoglobin levels in 16,001 individuals of European and Indian Asian ancestry. The most closely associated SNP (rs855791) results in nonsynonymous (V736A) change in the serine protease domain of TMPRSS6 and a blood hemoglobin concentration 0.13 (95% CI 0.09-0.17) g/dl lower per copy of allele A (P = 1.6 x 10(-13)). Our findings suggest that TMPRSS6, a regulator of hepcidin synthesis and iron handling, is crucial in hemoglobin level maintenance.

DOI10.1038/ng.462
Alternate JournalNat. Genet.
PubMed ID19820698
PubMed Central IDPMC3178047
Grant List1RL1MH083268-01 / MH / NIMH NIH HHS / United States
5R01HL087679-02 / HL / NHLBI NIH HHS / United States
BB/F020481/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
G0500539 / / Medical Research Council / United Kingdom
G0600705 / / Medical Research Council / United Kingdom
G0601966 / / Medical Research Council / United Kingdom
G0700931 / / Medical Research Council / United Kingdom
G0801056 / / Medical Research Council / United Kingdom
GR069224 / / Wellcome Trust / United Kingdom
R01 HL087679-02 / HL / NHLBI NIH HHS / United States
RL1 MH083268 / MH / NIMH NIH HHS / United States
RL1 MH083268-01 / MH / NIMH NIH HHS / United States
/ / British Heart Foundation / United Kingdom