• Dzana S Hukic, Urban Ösby, Eric Olsson, Agneta Hilding, Claes-Göran Östenson, Harvest F Gu, Ewa Ehrenborg, Gunnar Edman, Martin Schalling, Catharina Lavebratt, and Louise Frisén.
• Departments of aMolecular Medicine and Surgery, Neurogenetics Unit bNeurobiology, Care Sciences and Society, Centre for Family Medicine cClinical Neuroscience dMolecular Medicine and Surgery, Endocrine and Diabetes Unit eMedicine, Cardiovascular Medicine Unit, Karolinska Institutet fCenter for Molecular Medicine, Karolinska University Hospital Solna gDepartment of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB hChild and Adolescent Psychiatry Research Center, Stockholm, Sweden.
• Psychiatr. Genet. 2017 Dec 1; 27 (6): 210-218.

ObjectiveWe 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 MethodsWe 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.ResultsGenetic 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.ConclusionIncreased 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.

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