Association of OPRD1 Gene Variants with Changes in Body Weight and Psychometric Indicators in Patients with Eating Disorders

<b>Objectives</b>: This study aimed to investigate whether genetic variations in the <i>OPRD1</i> gene affect psychopathological symptoms and personality dimensions in eating disorders (ED) patients and/or contribute to ED risk. <b>Methods</b>: The study involved 221 female patients with anorexia nervosa (AN), 88 with bulimia nervosa (BN), and 396 controls. Sixteen tag-single nucleotide polymorphisms (SNPs) in <i>OPRD1</i> were identified. Psychometric evaluations were conducted using the Symptom Checklist 90 Revised (SCL-90R) and the Eating Disorders Inventory Test-2 (EDI-2). <i>p</i>-values obtained by regression models were corrected for multiple testing by the False Discovery Rate (FDR) method. <b>Results</b>: In AN patients, genotypes rs204077TT and rs169450TT were linked to lower body-mass index (BMI) values (FDR-q = 0.035 and 0.017, respectively), as was rs2234918 in a log-additive model (BMI: 18.0 ± 0.28, 17.22 ± 0.18 and 16.59 ± 0.39 for TT, TC and CC carriers, FDR-q = 0.012). Additionally, AN patients carrying the rs72665504AA genotype had higher scores in interpersonal distrust (FDR-q = 0.030), whilst BN carriers of rs513269TT and rs2873795TT showed lower scores in ineffectiveness (FDR-q = 0.041 and FDR-q = 0.021). In the AN group, BMI correlated with variability in a distal haplotype (rs508448/rs204077/rs223491, FDR-q = 0.028), which was also associated with the global positive symptom total (PST) index of SCL-90R (FDR-q = 0.048). Associations were more noticeable in BN patients; again, the distal region of the gene was linked to EDI-2 total scores (FDR-q = 0.004-0.048 for the four last haplotypes) and two global SCL-90R indices (GSI: FDR-q = 0.011 and positive symptom distress index (PSDI): FDR-q = 0.003 for the last s204077/rs2234918/rs169450 combination). No associations with ED risk were observed. <b>Conclusions</b>: Genetic variation in the <i>OPRD1</i> gene, particularly in its distal region, is associated with BMI and psychopathological comorbidities in ED patients.