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.

GAD2 gene sequence variations are associated with eating behaviors and weight gain in women from the Quebec family study.

The glutamate decarboxylase 2 (GAD2) gene encodes for the glutamic acid decarboxylase enzyme (GAD65), which is implicated in the formation of the gamma-aminobutyric acid (GABA), a neurotransmitter involved in the regulation of food intake. The objective of the present study was to test for association between GAD2 single-nucleotide polymorphisms (SNPs) and eating behaviors, dietary intake and obesity in subjects (n=873) from the Quebec Family Study (QFS). Energy and macronutrient intakes were measured using a 3-day dietary record and eating behaviors were assessed using the Three-Factor Eating Questionnaire (TFEQ). Six SNPs capturing about 90% of GAD2 gene variability were genotyped and tested for association with age- and BMI- adjusted phenotypes. No evidence of association was found in men. In women, a SNP (rs992990; c.61450 C>A) was associated with disinhibition (p=0.028), emotional susceptibility to disinhibition (p=0.0005) and susceptibility to hunger (p=0.028). Another SNP (rs7908975; c.8473A>C) was associated with carbohydrate (p=0.021) and lipid (p=0.021) intakes, disinhibition (p=0.011) and two of its subscales (emotional and situational susceptibility) as well as with avoidance of fattening foods (p=0.036). Six-year weight gain was two times higher in women carrying the variants associated with eating behaviors: 4.2kg (vs 2.1kg in non-carriers) in A-allele carriers of c.61450 C>A (p=0.038) and 4.9kg (vs 2.5kg in non-carriers) in C-allele carriers of c. 8473 A>C (p=0.013). The results suggest a role for the GAD2 gene in determining food intake, eating behaviors and weight gain over time in women.

Evidence of a quantitative trait locus for energy and macronutrient intakes on chromosome 3q27.3: the Quebec Family Study.

BACKGROUND: Little is known about the genes influencing dietary energy and nutrient intakes, despite evidence that these intakes are influenced by genetic factors. OBJECTIVE: We aimed to identify, by using a genome-wide linkage analysis, chromosomal regions harboring genes that affect energy and macronutrient intakes. DESIGN: Energy, carbohydrate, lipid, and protein intakes were assessed in 836 subjects from 217 families by using a 3-d dietary record. A total of 443 markers were genotyped and tested for linkage; age- and sex-adjusted energy and macronutrient intakes were expressed in grams and as percentages of total energy intake. Regression-based (Haseman-Elston) and variance-component (MERLIN) methods were applied to test for linkage with dietary data. A maximum of 454 sibpairs from 217 nuclear families were available for analysis. RESULTS: The genome scan provided suggestive evidence (P < or = 0.0023) for the presence of 6 quantitative trait linkages influencing total caloric and macronutrient intakes in the Québec Family Study. Of these, multiple linkages were found on chromosome 3q27.3, in a region harboring the adiponectin gene, at marker D3S1262 for energy [logarithm of odds (LOD): 2.24], carbohydrate (LOD: 2.00), and lipid (LOD: 1.65) intakes. The peak linkages for carbohydrate, lipid, and protein intakes were found on chromosomes 1p32.2 (LOD: 2.39), 1p35.2 (LOD: 2.41), and 10p15.3 (LOD: 2.72), respectively. The linkage results remained significant after adjustment for body mass index, which suggested that the genes underlying these quantitative trait linkages influence dietary intake independent of body size. CONCLUSION: The linkage on chromosome 3q27.3 with energy, lipid, and carbohydrate intakes suggests that this region of the genome may harbor genes that influence energy and macronutrient intakes in humans.