Analysis of Positive Selection at Single Nucleotide Polymorphisms Associated with Body Mass Index Does Not Support the ‘‘Thrifty Gene’’ Hypothesis

Guanlin Wang, John R Speakman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The ‘thrifty gene hypothesis’ suggests genetic susceptibility to obesity arises because of positive selection for alleles favored fat deposition and survival during famines. We used public domain data to locate signatures of positive selection based on derived allele frequency, genetic diversity, long haplotypes and differences between populations at single nucleotide polymorphisms (SNPs) identified in genome wide association studies (GWAS) for Body Mass Index (BMI). We used SNPs near the lactase (LCT), SLC24A5 and SLC45A2 genes as positive controls, and 120 randomly-selected SNPs as negative controls. We found evidence for positive selection (p<0.05) at nine out of 115 BMI SNPs. However, five of these involved positive selection for the protective allele (i.e. for leanness). The widespread absence of signatures of positive selection, combined with selection favoring leanness at some alleles, does not support the idea that obesity provided a selective advantage to survive historical periods of famine, or other selective advantage.
Original languageEnglish
Pages (from-to)531-541
Number of pages11
JournalCell Metabolism
Volume24
Issue number4
Early online date22 Sep 2016
DOIs
Publication statusPublished - 11 Oct 2016

Fingerprint

Single Nucleotide Polymorphism
Body Mass Index
Thinness
Alleles
Starvation
Genes
Obesity
Lactase
Public Sector
Genome-Wide Association Study
Genetic Predisposition to Disease
Gene Frequency
Haplotypes
Fats
Population

Keywords

  • obesity
  • positive selection
  • body mass index
  • BMI
  • single nucleotide polymorphisms (SNPs)
  • genome-wide association studies (GWASs)
  • thrifty gene hypothesis
  • drifty gene hypothesis

Cite this

@article{5c01ab05c09740f78e34fcf54bfcc5e9,
title = "Analysis of Positive Selection at Single Nucleotide Polymorphisms Associated with Body Mass Index Does Not Support the ‘‘Thrifty Gene’’ Hypothesis",
abstract = "The ‘thrifty gene hypothesis’ suggests genetic susceptibility to obesity arises because of positive selection for alleles favored fat deposition and survival during famines. We used public domain data to locate signatures of positive selection based on derived allele frequency, genetic diversity, long haplotypes and differences between populations at single nucleotide polymorphisms (SNPs) identified in genome wide association studies (GWAS) for Body Mass Index (BMI). We used SNPs near the lactase (LCT), SLC24A5 and SLC45A2 genes as positive controls, and 120 randomly-selected SNPs as negative controls. We found evidence for positive selection (p<0.05) at nine out of 115 BMI SNPs. However, five of these involved positive selection for the protective allele (i.e. for leanness). The widespread absence of signatures of positive selection, combined with selection favoring leanness at some alleles, does not support the idea that obesity provided a selective advantage to survive historical periods of famine, or other selective advantage.",
keywords = "obesity, positive selection, body mass index, BMI, single nucleotide polymorphisms (SNPs), genome-wide association studies (GWASs), thrifty gene hypothesis, drifty gene hypothesis",
author = "Guanlin Wang and Speakman, {John R}",
note = "Acknowledgments This work was supported by the National Natural Science Foundation of China (NSFC grant 91431102), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant XDB13030100), and the “1000 Talents Program.” We are grateful to all the members of the Molecular Energetics Group, especially Chaoqun Niu, for their support and discussion of the results and to Professor Wenfeng Qian for helpful discussion and constructive comments on the manuscript. We are grateful to three anonymous referees who made useful comments on the original submitted version, which greatly improved the paper.",
year = "2016",
month = "10",
day = "11",
doi = "10.1016/j.cmet.2016.08.014",
language = "English",
volume = "24",
pages = "531--541",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Analysis of Positive Selection at Single Nucleotide Polymorphisms Associated with Body Mass Index Does Not Support the ‘‘Thrifty Gene’’ Hypothesis

AU - Wang, Guanlin

AU - Speakman, John R

N1 - Acknowledgments This work was supported by the National Natural Science Foundation of China (NSFC grant 91431102), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant XDB13030100), and the “1000 Talents Program.” We are grateful to all the members of the Molecular Energetics Group, especially Chaoqun Niu, for their support and discussion of the results and to Professor Wenfeng Qian for helpful discussion and constructive comments on the manuscript. We are grateful to three anonymous referees who made useful comments on the original submitted version, which greatly improved the paper.

PY - 2016/10/11

Y1 - 2016/10/11

N2 - The ‘thrifty gene hypothesis’ suggests genetic susceptibility to obesity arises because of positive selection for alleles favored fat deposition and survival during famines. We used public domain data to locate signatures of positive selection based on derived allele frequency, genetic diversity, long haplotypes and differences between populations at single nucleotide polymorphisms (SNPs) identified in genome wide association studies (GWAS) for Body Mass Index (BMI). We used SNPs near the lactase (LCT), SLC24A5 and SLC45A2 genes as positive controls, and 120 randomly-selected SNPs as negative controls. We found evidence for positive selection (p<0.05) at nine out of 115 BMI SNPs. However, five of these involved positive selection for the protective allele (i.e. for leanness). The widespread absence of signatures of positive selection, combined with selection favoring leanness at some alleles, does not support the idea that obesity provided a selective advantage to survive historical periods of famine, or other selective advantage.

AB - The ‘thrifty gene hypothesis’ suggests genetic susceptibility to obesity arises because of positive selection for alleles favored fat deposition and survival during famines. We used public domain data to locate signatures of positive selection based on derived allele frequency, genetic diversity, long haplotypes and differences between populations at single nucleotide polymorphisms (SNPs) identified in genome wide association studies (GWAS) for Body Mass Index (BMI). We used SNPs near the lactase (LCT), SLC24A5 and SLC45A2 genes as positive controls, and 120 randomly-selected SNPs as negative controls. We found evidence for positive selection (p<0.05) at nine out of 115 BMI SNPs. However, five of these involved positive selection for the protective allele (i.e. for leanness). The widespread absence of signatures of positive selection, combined with selection favoring leanness at some alleles, does not support the idea that obesity provided a selective advantage to survive historical periods of famine, or other selective advantage.

KW - obesity

KW - positive selection

KW - body mass index

KW - BMI

KW - single nucleotide polymorphisms (SNPs)

KW - genome-wide association studies (GWASs)

KW - thrifty gene hypothesis

KW - drifty gene hypothesis

U2 - 10.1016/j.cmet.2016.08.014

DO - 10.1016/j.cmet.2016.08.014

M3 - Article

VL - 24

SP - 531

EP - 541

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -