caa a22 4500 445861657 CHVBK 20180317145445.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s00439-010-0935-z doi (NATIONALLICENCE)springer-10.1007/s00439-010-0935-z 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 [Elektronische Daten] [Yann Klimentidis, Marshall Abrams, Jelai Wang, Jose Fernandez, David Allison] 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 60,000years, 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 (100-1,600kb) 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. Springer-Verlag, 2010 Klimentidis Yann Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut Abrams Marshall Department of Philosophy, University of Alabama at Birmingham, Birmingham, USA aut Wang Jelai Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut Fernandez Jose Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut Allison David Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut Human Genetics Springer-Verlag 129/4(2011-04-01), 407-418 0340-6717 129:4<407 2011 129 439 https://doi.org/10.1007/s00439-010-0935-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0935-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Klimentidis Yann Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut NATIONALLICENCE 700 1- Abrams Marshall Department of Philosophy, University of Alabama at Birmingham, Birmingham, USA aut NATIONALLICENCE 700 1- Wang Jelai Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut NATIONALLICENCE 700 1- Fernandez Jose Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut NATIONALLICENCE 700 1- Allison David Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd., RPHB 327, 35294, Birmingham, AL, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/4(2011-04-01), 407-418 0340-6717 129:4<407 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer