Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans

Jin Li, Leslie A. Lange, Qing Duan, Yurong Lu, Andrew B. Singleton, Alan B. Zonderman, Michele K. Evans, Yun Li, Herman A. Taylor, Monte S. Willis, Mike Nalls, James G. Wilson, Ethan M. Lange

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Iron is an essential component of many important proteins and enzymes, including hemoglobin, which is responsible for carrying oxygen to the cells. African Americans (AAs) have a greater prevalence of iron deficiency compared with European Americans. We conducted genome-wide admixture-mapping and association studies for serum iron, serum ferritin, transferrin saturation (SAT) and total iron binding capacity (TIBC) in 2347 AAs participating in the Jackson Heart Study (JHS). Follow-up replication analyses for JHS iron-trait associated SNPs were conducted in 329 AA participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS). Higher estimated proportions of global African ancestry were significantly associated with lower levels of iron (P = 2.4 × 10-5), SAT (P = 0.0019) and TIBC (P = 0.042). We observed significant associations (P < 5 × 10-8) between serum TIBC levels and two independent SNPs around TF on chromosome 3, the first report of a genome-wide significant second independent signal in this region, and SNPs near two novel genes: HDGFL1 on chromosome 6 and MAF on chromosome 16. We also observed significant associations between ferritin levels and SNP snear GAB3 on chromosome X. We replicated our two independent associations at TF and our association at GAB3 in HANDLS. Our study provides evidence for both shared and unique genetic risk factors that are associated with iron-related measures in AAs. The top two variants inTF explain 11.2% of the total variation in TIBC levels in AAs after accounting for age, gender, body mass index and background ancestry.

Original languageEnglish (US)
Article numberddu454
Pages (from-to)572-581
Number of pages10
JournalHuman molecular genetics
Volume24
Issue number2
DOIs
StatePublished - Jan 15 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Li, J., Lange, L. A., Duan, Q., Lu, Y., Singleton, A. B., Zonderman, A. B., Evans, M. K., Li, Y., Taylor, H. A., Willis, M. S., Nalls, M., Wilson, J. G., & Lange, E. M. (2015). Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans. Human molecular genetics, 24(2), 572-581. [ddu454]. https://doi.org/10.1093/hmg/ddu454