A genome-wide association analysis of serum iron concentrations.

Tanaka T, Roy CN, Yao W, Matteini A, Semba RD, Arking D, Walston JD, Fried LP, Singleton A, Guralnik J, Abecasis GR, Bandinelli S, Longo DL and Ferrucci L

Blood (2010) 115:94-96

To investigate genetic variants that affect iron plasma 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 (BLSA, N=713). The top two SNPs were examined for replication in the Women's Health and Aging Study (WHAS I & II, N=569). The SNP most strongly associated with lower serum iron concentration was rs4820268 (p=5.12x10^-9) located in exon13 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.