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.
Highlights
Humans take in energy through protein, fat, and carbohydrate and expend energy in basal metabolism, thermogenesis, and physical activity [1, 2]
The study population for this analysis consists of participants with genotyping data from 11 nested case-control studies of various disease outcomes conducted in the three cohorts since 2007, who had adequately completed at least two food frequency questionnaires (FFQ) since 1986 for Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) and 1991 for Nurses’ Health Study II (NHS II)
The average reported energy intake was significantly lower than energy expenditure (P < 0.001) as has been previously reported [52]
Summary
Humans take in energy through protein, fat, and carbohydrate and expend energy in basal metabolism (reflecting by basic metabolic rate), thermogenesis, and physical activity [1, 2]. Body weight remains stable if energy intake equals energy expenditure; weight increases when energy intake
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