Association between olfactory receptor genes, eating behavior traits and adiposity: Results from the Quebec Family Study

Obesity is a major health problem that can be influenced by eating behaviors. Evidence suggests that the sensory properties of food influence eating behaviors and lead to overeating and overweight. A previous genome-wide linkage scan for eating behavior traits assessed with the Three-Factor Eating Questionnaire (cognitive dietary restraint, disinhibition and hunger) performed in the Quebec Family Study (QFS) revealed a quantitative trait locus for disinhibition on chromosome 19p13. This region encodes a cluster of seven olfactory receptor (OR) genes, including OR7D4, previously associated with odor perceptions. Direct sequencing of the OR7D4 gene revealed 16 sequence variants. Nine OR7D4 sequence variants with minor allele frequency (MAF) > 1% as well as 100 SNPs spanning the cluster of OR genes on 19p13 were tested for association with age- and sex-adjusted eating behaviors as well as adiposity traits in 890 subjects. One OR7D4 sequence variant (rs2878329 G > A) showed evidence of association with reduced levels of adiposity (p = 0.03), cognitive dietary restraint (p = 0.05) and susceptibility to hunger (p = 0.008). None of the OR7D4 SNPs was associated with disinhibition, but a SNP (rs2240927) in another OR gene (OR7E24) showed evidence of association (p = 0.03). Another SNP in the OR7G3 gene (rs10414255) was also found to be associated with adiposity and eating behaviors. These results are the first to suggest that variations in human olfactory receptor genes can influence eating behaviors and adiposity. The associations reported in the present study should be interpreted with caution considering the number of tests performed and considered as potential new hypotheses about the effects OR polymorphisms on eating behaviors and obesity that need to be further explored in other populations.

► We sequenced the OR7D4 gene in the Quebec family study. ► We found 16 SNPs with minor allele frequencies ranging from 0.1% to 17%. ► SNPs in 7 OR genes were tested for association with adiposity and eating behaviors. ► rs2878329 from OR7D4 was associated with adiposity and dietary restraint. ► OR7G3, OR7G1 and OR7E24 were also associated with eating behaviors or adiposity.