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The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤12 µg/L (cases) and controls (SF >100 µg/L in men, SF >50 µg/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the  TF  and  TMPRSS6  genes, and on chromosome 18q21. A novel SNP rs1421312 in  TMPRSS6  was associated with serum iron in whites (p = 3.7×10 −6 ) and replicated in African Americans (p = 0.0012).Twenty SNPs in the  TF  gene region were associated with total iron-binding capacity in whites (p<4.4×10 −5 ); six SNPs replicated in other ethnicities (p<0.01). SNP rs10904850 in the  CUBN  gene on 10p13 was associated with serum iron in African Americans (P = 1.0×10 −5 ). These results confirm known associations with iron measures and give unique evidence of their role in different ethnicities, suggesting origins in a common founder.

Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations