Association of the fat mass and obesity-associated gene risk allele, rs9939609A, and reward-related brain structures

Objective Recently, the fat mass and obesity-associated gene (FTO) has been identified as a genetic risk factor for developing obesity. The underlying mechanisms remain speculative. SNPs within FTO have been associated with brain atrophy in frontal and occipital regions, suggesting that FTO might affect body weight through cerebral pathways. Behavioral studies suggested a relationship between FTO and the reward-related behavioral traits. Therefore the relationship between the FTO risk allele rs9939609A and volumes of reward-related brain structures has been investigated. Methods Four hundred and ninety-two Dutch individuals (56% males, age: 70-82 years) participating in the PROSPER study underwent a 3D-T1-weighted MRI to assess the volumes of reward-related brain structures (e.g., amygdala, nucleus accumbens) and of gray matter and white matter. Linear regression analysis was performed to test for the association of subcortical and cortical structures with rs9939609A. Results rs9939609A is associated with lower volumes of the nucleus accumbens (p=0.03) and trended toward lower cortical gray matter volumes (p=0.08). This association is independent of gender, age, and BMI, FDR corrected. Conclusions The FTO risk allele is associated with lower nucleus accumbens volumes, suggesting that the higher body weight of risk-allele carriers might be due to changes within reward-related brain structures.