Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

Abstract

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Figure 1

Detailed results of the associations between SNPs within TMPRSS6 and transferring saturation in the adolescent cohort: (a) The genomic location of TMPRSS6 at 22q12-q13 on Chromosome 22; (b) −log₁₀(P) of the association tests between SNPs and transferring saturation, where red dots indicate genome-wide significant SNPs. rs2160906 has a significant cis-acting effect on TMPRSS6 expression (P = 8.4×10⁻⁸) ; (c) Linkage disequilibrium (LD) (r²) between rs855791 and all other HapMap SNPs within TMPRSS6; (d) HapMap-LD plot (r²) between genotyped SNPs within TMPRSS6.