title: Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans.
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 SNPs near 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 in TF explain 11.2% of the total variation in TIBC levels in AAs after accounting for age, gender, body mass index and background ancestry.
authors.affiliation: Department of Genetics.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Genetics.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Department of Genetics.
authors.forename: Qing
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of Genetics.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Laboratory of Neurogenetics.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Laboratory of Personality and Cognition and.
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.affiliation: Health Disparities Unit, National Institute on Aging, National Institutes of Health, Bethesda, MD 21225, USA.
authors.forename: Michele K
authors.initials: MK
authors.lastname: Evans
authors.affiliation: Department of Genetics Department of Biostatistics and.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medicine and School of Health Sciences, Jackson State University, Jackson, MS 39217, USA and Division of Natural Science, Tougaloo College, Tougaloo, MS 39174, USA.
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Monte S
authors.initials: MS
authors.lastname: Willis
authors.affiliation: Laboratory of Neurogenetics.
authors.forename: Mike
authors.initials: M
authors.lastname: Nalls
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.affiliation: Department of Genetics Department of Biostatistics and elange@med.unc.edu.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood* / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014168:Transferrin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014168:Transferrin; D005293:Ferritins; D007501:Iron