TY - JOUR
T1 - Revisiting the thrifty gene hypothesis via 65 loci associated with susceptibility to type 2 diabetes
AU - Ayub, Qasim
AU - Moutsianas, Loukas
AU - Chen, Yuan
AU - Panoutsopoulou, Kalliope
AU - Colonna, Vincenza
AU - Pagani, Luca
AU - Prokopenko, Inga
AU - Ritchie, Graham R.S.
AU - Tyler-Smith, Chris
AU - McCarthy, Mark I.
AU - Zeggini, Eleftheria
AU - Xue, Yali
N1 - Funding Information:
This work was supported by The Wellcome Trust (grant 098051 to Q.A., Y.C., K.P., V.C., L.P., G.R.S.R., C.T.-S., E.Z., and Y.X.; grants 098381 and WT090367MA to M.I.M.) and by Framework 7: ENGAGE (HEALTH-F4-2007- 201413 to M.I.M.).
PY - 2014/2/6
Y1 - 2014/2/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84893730773&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2013.12.010
DO - 10.1016/j.ajhg.2013.12.010
M3 - Article
C2 - 24412096
AN - SCOPUS:84893730773
SN - 0002-9297
VL - 94
SP - 176
EP - 185
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -
