A genome-wide association analysis of serum iron concentrations.
To investigate genetic variants that affect iron concentrations in persons not affected by overt genetic disorders of iron metabolism, a genome-wide association study was conducted in the InCHIANTI Study (N = 1206) and the Baltimore Longitudinal Study of Aging (N = 713). The top 2 single-nucleotide polymorphisms were examined for replication in the Women's Health and Aging Study (WHAS) I and II (N = 569). The single-nucleotide polymorphism most strongly associated with lower serum iron concentration was rs4820268 (P = 5.12 x 10(-9)), located in exon 13 of the transmembrane protease serine 6 (TMPRSS6) gene, an enzyme that promotes iron absorption and recycling by inhibiting hepcidin antimicrobial peptide transcription. The allele associated with lower iron concentrations was also associated with lower hemoglobin levels, smaller red cells, and more variability in red cell size (high red blood cell distribution width). Our results confirm the association of TMPRSS6 variants with iron level and provide further evidence of association with other anemia-related phenotypes.
Tanaka
Toshiko
T
MedStar Research Institute, Baltimore, MD, USA. tanakato@mail.nih.gov
Roy
Cindy N
CN
Yao
Wenliang
W
Matteini
Amy
A
Semba
Richard D
RD
Arking
Dan
D
Walston
Jeremy D
JD
Fried
Linda P
LP
Singleton
Andrew
A
Guralnik
Jack
J
Abecasis
Gonçalo R
GR
Bandinelli
Stefania
S
Longo
Dan L
DL
Ferrucci
Luigi
L
D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012697:Serine Endopeptidases / Q000235:genetics
D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human