Human Genetics

, Volume 129, Issue 4, pp 407–418

Natural selection at genomic regions associated with obesity and type-2 diabetes: East Asians and sub-Saharan Africans exhibit high levels of differentiation at type-2 diabetes regions

  • Yann C. Klimentidis
  • Marshall Abrams
  • Jelai Wang
  • Jose R. Fernandez
  • David B. Allison
Original Investigation

DOI: 10.1007/s00439-010-0935-z

Cite this article as:
Klimentidis, Y.C., Abrams, M., Wang, J. et al. Hum Genet (2011) 129: 407. doi:10.1007/s00439-010-0935-z

Abstract

Different populations suffer from different rates of obesity and type-2 diabetes (T2D). Little is known about the genetic or adaptive component, if any, that underlies these differences. Given the cultural, geographic, and dietary variation that accumulated among humans over the last 60,000 years, we examined whether loci identified by genome-wide association studies for these traits have been subject to recent selection pressures. Using genome-wide SNP data on 938 individuals in 53 populations from the Human Genome Diversity Panel, we compare population differentiation and haplotype patterns at these loci to the rest of the genome. Using an “expanding window” approach (100–1,600 kb) for the individual loci as well as the loci as ensembles, we find a high degree of differentiation for the ensemble of T2D loci. This differentiation is most pronounced for East Asians and sub-Saharan Africans, suggesting that these groups experienced natural selection at loci associated with T2D. Haplotype analysis suggests an excess of obesity loci with evidence of recent positive selection among South Asians and Europeans, compared to sub-Saharan Africans and Native Americans. We also identify individual loci that may have been subjected to natural selection, such as the T2D locus, HHEX, which displays both elevated differentiation and extended haplotype homozygosity in comparisons of East Asians with other groups. Our findings suggest that there is an evolutionary genetic basis for population differences in these traits, and we have identified potential group-specific genetic risk factors.

Supplementary material

439_2010_935_MOESM1_ESM.doc (584 kb)
Supplementary material 1 (DOC 583 kb)

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Yann C. Klimentidis
    • 1
  • Marshall Abrams
    • 2
  • Jelai Wang
    • 1
  • Jose R. Fernandez
    • 1
    • 3
  • David B. Allison
    • 1
    • 3
  1. 1.Section on Statistical Genetics, Department of BiostatisticsUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of PhilosophyUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Department of Nutrition SciencesUniversity of Alabama at BirminghamBirminghamUSA

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