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 γ-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: 4.2 kg (vs 2.1 kg in non-carriers) in A-allele carriers of c.61450 C > A (p = 0.038) and 4.9 kg (vs 2.5 kg 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.