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Can evidence from genome-wide association studies and positive natural selection surveys be used to evaluate the thrifty gene hypothesis in East Asians?

Koh XH, Liu X, Teo YY - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore.

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.

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Related in: MedlinePlus

Long haplotypes around THADA in East Asian and European populations.Illustration of haplotype forms identified by haploPS that span the longest genetic distances around THADA (brown horizontal bar) on chromosome 2. Uncharacteristically long haplotypes were found at the same frequency of 45% in two East Asian populations (CHD, CHS) to span THADA, whereas at the same frequency, the longest haplotypes present in European populations (CEU, TSI, MXL) were comparatively much shorter. The haplotypes for the two East Asian populations also carried the thymine allele at rs7578597 that has been reported in association studies to increase the risk to Type 2 diabetes.
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pone-0110974-g001: Long haplotypes around THADA in East Asian and European populations.Illustration of haplotype forms identified by haploPS that span the longest genetic distances around THADA (brown horizontal bar) on chromosome 2. Uncharacteristically long haplotypes were found at the same frequency of 45% in two East Asian populations (CHD, CHS) to span THADA, whereas at the same frequency, the longest haplotypes present in European populations (CEU, TSI, MXL) were comparatively much shorter. The haplotypes for the two East Asian populations also carried the thymine allele at rs7578597 that has been reported in association studies to increase the risk to Type 2 diabetes.

Mentions: For THADA, the T2D risk allele was located on the positively selected haplotype identified by haploPS (Figure 1, Table 2). The evidence of positive selection was present in two of the four East Asian populations (CHD, CHS), and the selected haplotype forms from both populations were identical with a haplotype similarity index (HSI) of 1.00. We observed that haploPS inferred the frequency of the selected haplotype to be 45% for both populations, although the frequencies of the risk alleles were at 99.4% and 100% in CHD and CHS respectively. However, it was noted that the associated risk allele was in fact an ancestral allele identical to that found in the chimpanzee genome.


Can evidence from genome-wide association studies and positive natural selection surveys be used to evaluate the thrifty gene hypothesis in East Asians?

Koh XH, Liu X, Teo YY - PLoS ONE (2014)

Long haplotypes around THADA in East Asian and European populations.Illustration of haplotype forms identified by haploPS that span the longest genetic distances around THADA (brown horizontal bar) on chromosome 2. Uncharacteristically long haplotypes were found at the same frequency of 45% in two East Asian populations (CHD, CHS) to span THADA, whereas at the same frequency, the longest haplotypes present in European populations (CEU, TSI, MXL) were comparatively much shorter. The haplotypes for the two East Asian populations also carried the thymine allele at rs7578597 that has been reported in association studies to increase the risk to Type 2 diabetes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206456&req=5

pone-0110974-g001: Long haplotypes around THADA in East Asian and European populations.Illustration of haplotype forms identified by haploPS that span the longest genetic distances around THADA (brown horizontal bar) on chromosome 2. Uncharacteristically long haplotypes were found at the same frequency of 45% in two East Asian populations (CHD, CHS) to span THADA, whereas at the same frequency, the longest haplotypes present in European populations (CEU, TSI, MXL) were comparatively much shorter. The haplotypes for the two East Asian populations also carried the thymine allele at rs7578597 that has been reported in association studies to increase the risk to Type 2 diabetes.
Mentions: For THADA, the T2D risk allele was located on the positively selected haplotype identified by haploPS (Figure 1, Table 2). The evidence of positive selection was present in two of the four East Asian populations (CHD, CHS), and the selected haplotype forms from both populations were identical with a haplotype similarity index (HSI) of 1.00. We observed that haploPS inferred the frequency of the selected haplotype to be 45% for both populations, although the frequencies of the risk alleles were at 99.4% and 100% in CHD and CHS respectively. However, it was noted that the associated risk allele was in fact an ancestral allele identical to that found in the chimpanzee genome.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore.

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.

Show MeSH
Related in: MedlinePlus