Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.
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.
Chambers
John C
JC
Department of Epidemiology and Public Health, Imperial College London, London, UK. john.chambers@ic.ac.uk
Zhang
Weihua
W
Li
Yun
Y
Sehmi
Joban
J
Wass
Mark N
MN
Zabaneh
Delilah
D
Hoggart
Clive
C
Bayele
Henry
H
McCarthy
Mark I
MI
Peltonen
Leena
L
Freimer
Nelson B
NB
Srai
Surjit K
SK
Maxwell
Patrick H
PH
Sternberg
Michael J E
MJ
Ruokonen
Aimo
A
Abecasis
Gonçalo
G
Jarvelin
Marjo-Riitta
MR
Scott
James
J
Elliott
Paul
P
Kooner
Jaspal S
JS
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
D006454:Hemoglobins; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human