A genome-wide association study of energy intake and expenditure

Abstract

Excessive energy intake or insufficient energy expenditure, which result in energy imbalance, contribute to the development of obesity. Obesity-related genes, such as FTO, are associated with energy traits. No genome-wide association studies (GWAS) have been conducted to detect the genetic associations with energy-related traits, including energy intake and energy expenditure, among European-ancestry populations. In this study, we conducted a genome-wide study using pooled GWAS including 12,030 European-ancestry women and 6,743 European-ancestry men to identify genetic variants associated with these two energy traits. We observed a statistically significant genome-wide SNP heritability for energy intake of 6.05% (95%CI = (1.76, 10.34), P = 0.006); the SNP heritability for expenditure was not statistically significantly greater than zero. We discovered three SNPs on chromosome 12q13 near gene ANKRD33 that were genome-wide significantly associated with increased total energy intake among all men. We also identified signals on region 2q22 that were associated with energy expenditure among lean people. Body mass index related SNPs were found to be significantly associated with energy intake and expenditure through SNP set analyses. Larger GWAS studies of total energy traits are warranted to explore the genetic basis of energy intake, including possible differences between men and women, and the association between total energy intake and other downstream phenotypes, such as diabetes and chronic diseases.

Fig 1

A) QQ plot for the SNP effect on daily energy intake for men. B) Manhattan plot for the SNP effect on daily energy intake for men. C) LocusZoom plot of the region associated with daily energy intake among men on chromosome 12q13.

Fig 2

A) QQ plot for the SNP effect on daily energy expenditure for lean women and men. B) Manhattan plot for the SNP effect on daily energy expenditure for lean women and men. C) LocusZoom plot of the region associated with daily energy expenditure for lean women and men on chromosome 2q22.1.

Fig 3. Plot of the regression coefficients for the effect of BMI-increasing alleles on energy intake (and their 95% confidence intervals) as function of per-allele effect on BMI.

The marked SNPs in panel (a) are: 1, rs11583200 (Chr 1:50559820); 2, rs9400239 (Chr 6:108977663); 3, rs11126666 (Chr 2:26928811); 4, rs17405819 (Chr 8:76806584); 5, rs3101336 (Chr 1:72751185); 6, rs10938397 (Chr 4:45182527); 7, rs1516725 (Chr3:185824004).