Variants in the Obesity-Linked FTO gene locus modulates psychopathological features of patients with Anorexia Nervosa

[Display omitted] •FTO is the strongest locus for obesity known but has barely been tested in ED.•FTO variants were not related to the risk of ED.•FTO haplotypes were related to several personality dimensions shown by AN patients.•A distal region of FTO was linked to anxiety and depression in AN patients.•FTO was revealed as an important locus for psychopathology in AN patients. Our aim was to determine whether variability in the fat mass obesity (FTO) gene locus, consistently related to obesity, affects the risk of eating disorders (ED) and/or the psychopathology displayed by these patients. We analyzed 26 tag-single nucleotide polymorphisms (SNPs) that capture FTO variability in 352 ED patients [233 with Anorexia Nervosa (AN) and 119 with binge-eating] and 396 controls. Psychopathological symptoms and traits were evaluated by the Eating Disorders Inventory Test 2 (EDI-2) and Symptoms Checklist 90 Revised (SCL-90R) questionnaires. No associations were found for ED risk. The rs7205987 CC genotype correlated with higher scores in all but one of the EDI-2 scales in the AN group. Associations with Bulimia (p = 0.0019) and Interoceptive Awareness (p = 0.00007) retained significance after False Discovery Rate (FDR) correction for multiple testing. A 3-SNP sliding window analysis showed that FTO haplotypes were again highly associated with Interoceptive Awareness (rs9921255/rs6499662/rs7205987 haplotype; FDR-q = 0.04), Bulimia (rs1125338/rs2192872/rs708258; FDR-q = 0.00037), and Maturity Fears (rs708258/rs12599672/rs11076017; FDR-q = 0.041). In addition, a distal region of the gene between rs9924877 (position 53947509) and rs2192872 (54040715) was linked to Anxiety, Depression and Phobic Anxiety in AN patients, with FDR-q values ranging from 0.023 to 0.045. The results suggest that the FTO gene might be an important locus regarding traits and psychopathological symptoms often displayed by AN patients.