Abstract P254: Genome-wide Association and Admixture Study of Iron-related Phenotypes in African Americans

Abstract

Introduction: Iron deficiency is a heritable risk factor for various serious diseases, including cardiovascular disease (CVD). Genome-wide association studies (GWAS) have identified several variants associated with iron-related phenotypes in individuals of primarily European descent. African Americans (AA) have, on average, greater levels of iron deficiency compared to European Americans, but no large-scale genetic studies for iron-related phenotypes have been performed in individuals of African ancestry to date. Methods: We conducted genome-wide admixture mapping studies and GWASs for serum iron, serum ferritin, transferrin saturation (SAT), and total binding iron capacity (TIBC) in 2347 AA participating in the Jackson Heart Study (JHS). Results: Higher proportions of estimated global African ancestry were significantly associated with lower levels of iron (p=2.4x10 -5 ), SAT (p=0.0019) and TIBC (p=0.042) and a number of chromosomal regions were observed to have local ancestry estimates nominally associated with these measures. We observed significant associations (P < 5x10 -8 ) between serum TIBC levels and multiple independent single nucleotide polymorphisms (SNPs) around TF, a well-established region for iron and transferrin levels in Caucasians, and SNPs near two novel genes: HDGFL1 and MAF. In addition, we replicated four other established loci in our AA samples including SLC17A1 , HFE , HIST1H2BJ and TMPRSS6 . Conclusions: 1) We observed SNPs in or near three genes, TF , HDGFL1 and MAF that were significantly associated with TIBC in AA. 2) We observed that both global and local genetic admixture are important predictors of iron measures in AA, further implicating the importance of certain genetic risk factors in the AA population. 3) We have also replicated four other established loci in our AA samples demonstrating the importance of some genetic risk factors for iron related measure across multiple populations. Future fine-mapping studies, incorporating less common variants, and functional studies should be undertaken to better characterize these loci and to ultimately identify the functional variants directly influencing TIBC levels in AA.