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. 2011 Apr;129(4):407-18.
doi: 10.1007/s00439-010-0935-z. Epub 2010 Dec 28.

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  1 , Marshall Abrams, Jelai Wang, Jose R Fernandez, David B Allison
Affiliations

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 et al. Hum Genet. 2011 Apr.

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.

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Figures

Figure 1
Figure 1
Mean percentile of global (7-way) FST across all 16 loci by window size. Horizontal dashed line indicates 95th percentile cut-off (0.614), and horizontal dotted line indicates 99th percentile cutoff (0.668).
Figure 2
Figure 2
Mean percentile of GSFST across all 16 loci by window size for obesity (A) and T2D (B). Dashed horizontal line indicates 95% percentile cutoff (0.614), and horizontal solid line indicates 99th percentile cutoff (0.668). (AFR: Sub-Saharan Africa, MID: Middle East, SAS: South Asia, EUR: Europe, EAS: East Asia, OCE:Oceania, AME:America)
Figure 3
Figure 3
A) Pair-wise FST percentiles for the 100 kb window surrounding NEGR1, B) GSFST across different window sizes for NEGR1. (AFR: Sub-Saharan Africa, MID: Middle East, SAS: South Asia, EUR: Europe, EAS: East Asia, OCE:Oceania, AME:America)
Figure 4
Figure 4
A) Pair-wise FST percentiles for the 1600 kb window surrounding HHEX, B) GSFST across different window sizes for HHEX. C) XP-EHH in 500 kb window surrounding HHEX risk SNP, from the HGDP Genome Browser, where the y-axis represents the −log10 of the empirical p-value for a window centered at the SNP. (AFR: Sub-Saharan Africa, MID: Middle East, SAS: South Asia, EUR: Europe, EAS: East Asia, OCE:Oceania, AME:America)
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