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Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin ( N  = 246,139), total iron binding capacity ( N  = 135,430), iron ( N  = 163,511) and transferrin saturation ( N  = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at  DUOX2 ,  F5 ,  SLC11A2  and  TMPRSS6  associate with iron deficiency anemia, while variants at  TF ,  HFE ,  TFR2  and  TMPRSS6  associate with iron overload. A  HBS1L-MYB  intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The  DUOX2  missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.

A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis