title: A genome-wide association analysis of serum iron concentrations.
abstract: 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.
authors.affiliation: MedStar Research Institute, Baltimore, MD, USA. tanakato@mail.nih.gov
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Cindy N
authors.initials: CN
authors.lastname: Roy
authors.forename: Wenliang
authors.initials: W
authors.lastname: Yao
authors.forename: Amy
authors.initials: A
authors.lastname: Matteini
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.forename: Dan
authors.initials: D
authors.lastname: Arking
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Jack
authors.initials: J
authors.lastname: Guralnik
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human