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

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42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)407-418
Number of pages12
JournalHuman Genetics
Volume129
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

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Genetic Selection
Type 2 Diabetes Mellitus
Obesity
Haplotypes
Genome
Population
North American Indians
Genome-Wide Association Study
Population Genetics
Human Genome
African Americans
Single Nucleotide Polymorphism
Pressure

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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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. / Klimentidis, Yann C; Abrams, Marshall; Wang, Jelai; Fernandez, Jose R.; Allison, David B.

In: Human Genetics, Vol. 129, No. 4, 04.2011, p. 407-418.

Research output: Contribution to journalArticle

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