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.
Hum Genet
; 129(4): 407-18, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21188420
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Seleção Genética
/
Diabetes Mellitus Tipo 2
/
Estudo de Associação Genômica Ampla
/
Obesidade
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Africa
/
Asia
Idioma:
En
Revista:
Hum Genet
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos