Genetic variants of increased waist circumference in psychosis.

Objective: We examined whether established metabolic risk genetic variants in the population confer a risk for increased waist circumference in patients with schizophrenia spectrum disorders and also an association with schizophrenia spectrum disorders irrespective of waist circumference.

Patients And Methods: We analyzed the association in (i) a case-case model in which patients with schizophrenia spectrum disorder with increased waist circumference (≥80 cm for women and ≥94 cm for men) (n=534) were compared with patients with normal waist circumference (<80 cm for women; <94 cm for men) (n=124), and in (ii) a case-control model in which schizophrenia spectrum disorder patients with increased waist circumference or irrespective of waist circumference were compared with population-derived controls (n=494) adjusted for age, sex, fasting glucose, smoking, and family history of diabetes.

Results: Genetic variants in five genes (MIA3, MRAS, P2RX7, CAMKK2, and SMAD3) were associated with increased waist circumference in patients with schizophrenia spectrum disorder (P<0.046). Genetic variants in three other genes (PPARD, MNTR1B, and NOTCH2) were associated with increased waist circumference in patients when compared with control individuals (P<0.037). Genetic variants in the PPARD, MNTR1B, NOTCH2, and HNF1B were nominally associated with schizophrenia spectrum disorder irrespective of waist circumference (P<0.027). No differences in waist circumference between specific psychosis diagnoses were detected.

Conclusion: Increased waist circumference in patients with schizophrenia spectrum disorder may be explained, in part, by increased metabolic risk gene burden, and it indicates a shared genetic susceptibility to metabolic disorder and psychosis per se. Along these lines, common metabolic risk genetic variants confer a risk for increased waist circumference in patients with schizophrenia spectrum disorders.