Inverse association of the obesity predisposing FTO rs9939609 genotype with alcohol consumption and risk for alcohol dependence

Aims To investigate whether the FTO rs9939609 A allele (a risk factor for obesity) is associated with measures of alcohol consumption. Design Population-based cross-sectional study and two case-control studies. Setting Poland and the Warsaw area. Participants A total of 6584 subjects from the WOBASZ survey and two cohorts of alcohol-dependent patients (n = 145 and n = 148). Measurements Questionnaire data analysis, rs9939609 typing. Findings Among individuals drinking alcohol, the obesity-associated AA genotype was also associated with lower total ethanol consumption [sex-, age- and body mass index (BMI)-adjusted difference: 0.21 g/day, P = 0.012] and distinct drinking habits with relatively low frequency of drinks but larger volume consumed at a time as evidenced by (i) association between AA and frequency/amount of typical drinks (P = 0.023, multiple logistic regression analysis); (ii) inverse correlation between AA and drink frequency adjusted for drink size (P = 0.007 for distilled spirits, P = 0.018 for beer); (iii) decreased frequency of AA [odds ratio (OR) = 0.46, P = 0.0004] among those who drank small amounts of distilled spirits (< 100 ml at a time) but frequently (>= 1-2 times/week). A decrease of AA was also found in both cohorts of alcohol-dependent patients versus geographically matched subjects from WOBASZ yielding a pooled estimate of OR = 0.59, confidence interval (CI): 0.40-0.88, P = 0.008. Exploratory analysis showed that those with rs9939609 AA reported lower (by 1.22) mean number of cigarettes/day during a year of most intense smoking (P = 0.003) and were older at start of smoking by 0.44 years (P = 0.016). Conclusions The FTO AA genotype, independently from its effect on BMI, is associated with measures of ethanol consumption and possibly tobacco smoking.