title: Can evidence from genome-wide association studies and positive natural selection surveys be used to evaluate the thrifty gene hypothesis in East Asians?
abstract: Body fat deposition and distribution differ between East Asians and Europeans, and for the same level of obesity, East Asians are at higher risks of Type 2 diabetes (T2D) and other metabolic disorders. This observation has prompted the reclassifications of body mass index thresholds for the definitions of "overweight" and "obese" in East Asians. However, the question remains over what evolutionary mechanisms have driven the differences in adiposity morphology between two population groups that shared a common ancestor less than 80,000 years ago. The Thrifty Gene hypothesis has been suggested as a possible explanation, where genetic factors that allowed for efficient food-energy conversion and storage are evolutionarily favoured by conferring increased chances of survival and fertility. Here, we leveraged on the existing findings from genome-wide association studies and large-scale surveys of positive natural selection to evaluate whether there is currently any evidence to support the Thrifty Gene hypothesis. We first assess whether the existing genetic associations with obesity and T2D are located in genomic regions that are reported to be under positive selection, and if so, whether the risk alleles sit on the extended haplotype forms. In addition, we interrogate whether these risk alleles are the derived forms that differ from the ancestral alleles, and whether there is significant evidence of population differentiation at these SNPs between East Asian and European populations. Our systematic survey did not yield conclusive evidence to support the Thrifty Gene hypothesis as a possible explanation for the differences observed between East Asians and Europeans.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
authors.forename: Xuan-Han
authors.initials: XH
authors.lastname: Koh
authors.affiliation: NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: Xuanyao
authors.initials: X
authors.lastname: Liu
authors.affiliation: NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; Life Sciences Institute, National University of Singapore, Singapore, Singapore; Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
mesh_terms: D044466:Asian People / Q000235:genetics; D002681:China; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060148:HapMap Project; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic