Genes Associated with Increased Fasting Glucose in Patients with Schizophrenia Spectrum Disorders

Background: Metabolic risk factors represent a major cause of increased coronary heart disease morbidity and mortality among psychosis patients. Although antipsychotic medication may lead to hyperglycemia, an association to severe mental illness was established before the introduction of antipsychotics. Methods: We investigated the association between metabolic risk genes and elevated fasting glucose level in patients with schizophrenia spectrum disorder. We applied two association models; (i) case-case where psychosis patients with elevated fasting glucose level (≥5.6 mmol/l) or diagnosed diabetes (n=263) were compared to patients with normal glucose level (n=389), and (ii) case-control model where psychosis patients with elevated fasting glucose level were compared to population-derived controls (n=494). Association analyses were adjusted for age, sex, smoking, family history of diabetes, and waist circumference. (iii) We also investigated whether metabolic genes were associated with schizophrenia spectrum disorder independent of fasting glucose. Results: No differences between schizophrenia spectrum diagnoses regarding genetic associations with increased fasting glucose were detected. In a case-case model, a genetic variant in IGF2BP2 was associated with elevated fasting glucose level among persons with schizophrenia spectrum disorder. In a case-control model associations were found with genetic variants in the NOTCH2, THADA, WFS1, P2RX7, and MNTR1B. A genetic variant in PPARD was nominally associated with schizophrenia spectrum disorder independent of glucose level. Conclusion: Our findings indicate that common metabolic polymorphisms associated with elevated fasting glucose among schizophrenia spectrum disorder patients may at least partially be explained by increased vulnerability in schizophrenia spectrum disorders for genes associate with elevated fasting glucose in the population.