Revisiting the Thrifty Gene Hypothesis via 65 Loci Associated with Susceptibility to Type 2 Diabetes

被引：53

作者：

Ayub, Qasim ^{[1
]}

Moutsianas, Loukas ^{[2
]}

Chen, Yuan ^{[1
]}

Panoutsopoulou, Kalliope ^{[1
]}

Colonna, Vincenza ^{[1
,3
]}

Pagani, Luca ^{[1
]}

Prokopenko, Inga ^{[2
]}

Ritchie, Graham R. S. ^{[1
,4
]}

Tyler-Smith, Chris ^{[1
]}

McCarthy, Mark I. ^{[2
,5
,6
]}

Zeggini, Eleftheria ^{[1
]}

Xue, Yali ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Hinxton CB10 1HH, England

[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[3] Natl Res Council CNR, Inst Genet & Biophys, I-80125 Naples, Italy

[4] European Bioinformat Inst, Hinxton CB10 1SH, England

[5] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England

[6] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2014年 / 94卷 / 02期

基金：

英国惠康基金;

关键词：

POSITIVE SELECTION; VARIANTS; MELLITUS; GENOTYPE; SEQUENCE; HISTORY; DISEASE; IMPACT; KCNQ1;

D O I：

10.1016/j.ajhg.2013.12.010

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

We have investigated the evidence for positive selection in samples of African, European, and East Asian ancestry at 65 loci associated with susceptibility to type 2 diabetes (T2D) previously identified through genome-wide association studies. Selection early in human evolutionary history is predicted to lead to ancestral risk alleles shared between populations, whereas late selection would result in population-specific signals at derived risk alleles. By using a wide variety of tests based on the site frequency spectrum, haplotype structure, and population differentiation, we found no global signal of enrichment for positive selection when we considered all T2D risk loci collectively. However, in a locus-by-locus analysis, we found nominal evidence for positive selection at 14 of the loci. Selection favored the protective and risk alleles in similar proportions, rather than the risk alleles specifically as predicted by the thrifty gene hypothesis, and may not be related to influence on diabetes. Overall, we conclude that past positive selection has not been a powerful influence driving the prevalence of T2D risk alleles.

引用

页码：176 / 185

页数：10

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