title: Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.
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.
authors.affiliation: Department of Epidemiology and Public Health, Imperial College London, London, UK. john.chambers@ic.ac.uk
authors.forename: John C
authors.initials: JC
authors.lastname: Chambers
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Joban
authors.initials: J
authors.lastname: Sehmi
authors.forename: Mark N
authors.initials: MN
authors.lastname: Wass
authors.forename: Delilah
authors.initials: D
authors.lastname: Zabaneh
authors.forename: Clive
authors.initials: C
authors.lastname: Hoggart
authors.forename: Henry
authors.initials: H
authors.lastname: Bayele
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Freimer
authors.forename: Surjit K
authors.initials: SK
authors.lastname: Srai
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Michael J E
authors.initials: MJ
authors.lastname: Sternberg
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Abecasis
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.forename: James
authors.initials: J
authors.lastname: Scott
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Jaspal S
authors.initials: JS
authors.lastname: Kooner
mesh_terms: D001665:Binding Sites; D055162:Biocatalysis; D055106:Genome-Wide Association Study; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D006454:Hemoglobins; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human