Association of the 5-HT2c gene with susceptibility and minimum body mass index in anorexia nervosa

The association between a non-conservative Cys23Ser in the 5-HT2c gene and anorexia nervosa in females was examined. We used case-controls and family based association analysis in a sample of 118 patients with DSMIV anorexia nervosa, 244 controls and 47 family trios. There was a significant increase in the frequency of the Ser23 allele in the patients by allele (18.8% vs 12.8%; p = 0.026; OR 1.58, 95% Cl 1.0-2.4) and genotype (32.2% vs 19.9%; genotype-wise p = 0.027). There was significant correlation between genotype and minimum BMI (r(2) = 0.056; p = 0.01), indicating that the Ser23 allele has an effect on severity of illness. We performed TDT analysis using a sub-sample of the cases (58) for whom both parents were available and we found an excess transmission of the Ser23 allele (p = 0.05). Our findings are consistent a role for the Ser23 allele of 5-HT2c in mediating susceptibility to and increasing severity of anorexia nervosa.