Academic Journal
A genetic association study of iron absorption in adults of East Asian or Northern European ancestry from the Iron Genes in East Asian and Northern European Adults Study (FeGenes).
| Τίτλος: | A genetic association study of iron absorption in adults of East Asian or Northern European ancestry from the Iron Genes in East Asian and Northern European Adults Study (FeGenes). |
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| Συγγραφείς: | Barad A; Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States., Xu H; Department of Genetics, University of Georgia, Athens, GA, United States., Clark AG; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States; Department of Computational Biology, Cornell University, Ithaca, NY, United States., Gu Z; Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States., Pressman EK; Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY, United States., Ye K; Department of Genetics, University of Georgia, Athens, GA, United States; Institute of Bioinformatics, University of Georgia, Athens, GA, United States. Electronic address: kaixiong.ye@uga.edu., O'Brien KO; Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States. Electronic address: koo4@cornell.edu. |
| Πηγή: | The American journal of clinical nutrition [Am J Clin Nutr] 2026 Jun; Vol. 123 (6), pp. 101298. Date of Electronic Publication: 2026 Mar 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 0376027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-3207 (Electronic) Linking ISSN: 00029165 NLM ISO Abbreviation: Am J Clin Nutr Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2023- : [New York, NY] : Elsevier Original Publication: Bethesda, MD : American Society of Clinical Nutrition |
| Ιατρικοί όροι (MeSH): | East Asian People*/genetics , European People*/genetics , Intestinal Absorption*/genetics , Iron*/metabolism, Ferritins/blood ; Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Genetic Association Studies ; Genotype ; Polymorphism, Single Nucleotide |
| Περίληψη: | Background: Over 100 genetic variants are linked to iron (Fe) biomarkers in European populations, but their effects on nonheme Fe absorption remain unknown. Additionally, despite the higher body Fe burden observed in East Asian (EA) individuals, the genetic factors influencing Fe absorption in this population remain unexplored. Objectives: We aimed to examine the impact of genetic variation on Fe absorption and evaluate how it differs across individuals of genetically inferred Northern European (NE) or EA ancestry. Methods: Participants in this genetic association study were healthy males and premenopausal females of EA (n = 253) or NE (n = 251) ancestry, aged 18-50 y. Genotyping data were obtained using the Illumina Global Diversity Array. Fe absorption was assessed using the erythrocyte Fe isotope incorporation method, normalized to a serum ferritin (SF) of 40 μg/L. We evaluated the associations of candidate variants with SF-corrected Fe absorption, tested for variant-ancestry interaction effects, and assessed a European-derived polygenic score for SF (PGS-SF). Results: Seven variants nominally associated with SF-corrected Fe absorption in either EA or NE were tested for variant-ancestry interactions. Two variants remained significant after Bonferroni correction (P-interaction < 0.007), rs1672992 in hepsin and rs9423600 in urocortin 3 (UCN3), indicating ancestry-specific genetic effects on Fe absorption. The C allele of rs1672992 was associated with a 26% decrease in Fe absorption in NE (P = 0.04) but with a 62% increase in EA (P = 0.008). The G allele of rs9423600 was associated with a 27% decrease in Fe absorption in NE (P = 0.005) but with a nonsignificant 17% increase in EA (P = 0.18). The PGS-SF was significantly associated with SF-corrected Fe absorption in both groups (P < 0.05) but captured only a small proportion of its variance (NE: 1.8%, EA: 2.3%). Conclusions: Our findings underscore the need to further understand the genetic architecture of Fe metabolism across diverse populations to inform precision nutrition strategies aimed at reducing Fe-related chronic diseases. The study was registered at clinicaltrials.gov as NCT04198545. (Copyright © 2026 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Conflict of interest The authors report no conflicts of interest. |
| Grant Information: | R01 DK122216 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: East Asian populations; European populations; genetic associations; iron absorption; iron status |
| Molecular Sequence: | ClinicalTrials.gov NCT04198545 |
| Substance Nomenclature: | 9007-73-2 (Ferritins) E1UOL152H7 (Iron) |
| Entry Date(s): | Date Created: 20260327 Date Completed: 20260606 Latest Revision: 20260611 |
| Update Code: | 20260612 |
| PubMed Central ID: | PMC13173465 |
| DOI: | 10.1016/j.ajcnut.2026.101298 |
| PMID: | 41895699 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1938-3207 |
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| DOI: | 10.1016/j.ajcnut.2026.101298 |