Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry

PLoS One. 2016 Jun 22;11(6):e0157996. doi: 10.1371/journal.pone.0157996. eCollection 2016.

Abstract

Background: Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations.

Methods: We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels.

Results: In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only.

Conclusions: In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations.

MeSH terms

  • Adult
  • Black People / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Ferritins / genetics*
  • Gene Frequency / genetics
  • Genome-Wide Association Study*
  • Hemoglobins / genetics*
  • Humans
  • Iron / metabolism*
  • Male
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Hemoglobins
  • Ferritins
  • Iron

Grants and funding

The Kenyan cohort research was conducted within the framework of INSTAPA Project, funded by the European Union’s Seventh Framework Programme [FP7/2007-2013] under grant agreement nr 211484. The Tanzanian cohort research was supported through funding from the Netherlands Organisation for Scientific Research (NWO)/WOTRO [W93-413, WAO93-441, as well as WIZ93-465, UNICEF, Cornelis Visser Foundation and Wageningen University (Interdisciplinary Research and Education Fund). The PURE study was supported through grants provided by the South African Medical Research Council (Self-Initiated Research Grants), Cape Town, South Africa, with further support from a fellowship provided by Unilever R&D, Vlaardingen, The Netherlands, and from the European Union (EU) funded staff exchange European-South African Partnership in Nutrition Research program (grant MC-IRSES-2008-230786). The BLSA was supported through funding by the Intramural Research Program of the NIH, National Institute on Aging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.