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Genetics variants in the NEGR1 gene, strongly expressed in the brain, have been reported to affect the neuronal control of food intake therefore inducing obesity. With the same rationale, we hypothesized that this genetic variability may be associated with psychological traits commonly displayed by eating disorder (ED) patients and/or with the risk for the disorder. We analyzed 21 tag-single-nucleotide polymorphisms (SNPs) in the coding sequence and adjacent regions of the NEGR1 gene. A total of 169 ED patients (106 with anorexia nervosa (AN) and 63 with bulimia nervosa (BN)) and 312 healthy subjects were genotyped. Personality traits and general psychopathological symptoms were assessed by the Eating Disorders Inventory Test-2 (EDI-2) and Symptom Checklist 90 Revised inventories. None of the SNPs or haplotypes analyzed were associated with a greater risk of ED or correlated with anthropometric parameters. However, in patients with BN, four SNPs (rs12740031, rs10789322, rs6659202 and rs591540) correlated with the scores in Drive for Thinness (DT), Ineffectiveness (I) and Interoceptive Awareness (IA) (Bonferroni-P<0.05 in all instances). The first two SNPs along with rs954299 and rs2422021 formed a haplotype block, which showed a consistent association with the EDI-2 score in BN patients (Bonferroni-P=0.01). A subsequent three-SNP sliding-window approach identified a central area, encompassing both the haplotype block and the individually relevant SNPs that strongly correlated with the scores of BN patients in DT, I, IA and Bulimia. No associations were identified in the AN group. These preliminary results indicate that NEGR1 could be an important locus influencing certain personality dimensions in BN patients.

Introduction TFAP2B and KCTD15 are obesity‐related genes that interact to regulate feeding behavior. We hypothesize that variability in these loci, isolated or in combination, could also be related to the risk of eating disorders (ED) and/or associated psychological traits.MethodsWe screened 425 participants (169 ED patients, 75 obese subjects, and 181 controls) for 10 clinically relevant and tag single‐nucleotide polymorphisms (SNPs) in KCTD15 and TFAP2B by the Sequenom MassARRAY platform and direct sequencing. Psychometric evaluation was performed with EDI‐2 and SCL‐90R inventories.ResultsThe KCTD15 rs287103 T variant allele was associated with increased risk of bulimia nervosa (BN) (OR = 4.34 [1.47–29.52]; p = .003) and with scores of psychopathological scales of these patients. Haplotype *6 in KCTD15 was more frequent in controls (OR = 0.40 [0.20–0.80], p = .009 for anorexia nervosa), while haplotype *4 in TFAP2B affected all three scales of the SCL‐90R inventory in BN patients (p ≤ .01). Epistasis analyses revealed relevant interactions with body mass index of BN patients (p < .001). Genetic profiles in obese patients did not significantly differ from those found in ED patients.ConclusionsThis is the first study that evaluates the combined role of TFAP2B and KCTD15 genes in ED. Our preliminary findings suggest that the interaction of genetic variability in these loci could influence the risk for ED and/or anthropometric and psychological parameters.

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We aimed to determine whether variability in the melanocortin-4 receptor (MC4R) gene, predisposing to hyperphagia and obesity, may also be present in nonobese patients with binge-eating behavior or be related to anthropometric or psychopathological parameters in these patients. The coding region of the MC4R gene was sequenced in nonobese patients with binge-eating behavior diagnosed with bulimia nervosa or binge-eating disorder (n=77); individuals with severe early-onset obesity (n=170); and lean women with anorexia nervosa (n=20). A psychometric evaluation (Eating Disorders Inventory-2 and Symptom Checklist 90 Revised inventories) was carried out for all the patients with eating disorders. In the obesity group, 10 different variants were identified, whereas in the binge-eating patients, only two individuals with bulimia nervosa were found to carry the I251L polymorphism, which did not correlate with weight, BMI, or psychopathological features. We found no evidence that mutations in the MC4R gene are associated with binge-eating behavior in nonobese eating disorder patients.