Genetic risk for severe mental illness does not influence adipose tissue functions.

Abstract

Abstract Background: Psychiatric disorders are associated with an increased risk of metabolic diseases, including obesity. The aim of this study was to determine whether genetic variants associated with severe mental illness (individually or combined in polygenic risk scores) have significant associations with adipose tissue biology. Methods: Adipose phenotypes, clinical and genetic data from was available from the participants of the GENiAL study. Summary statistics from the Psychiatric Genomic Consortium genome-wide association study meta-analyses were used to calculate polygenic risk scores for major depressive disorder, bipolar disorder and schizophrenia. Individual genetic variants associated with major depressive disorder, bipolar disorder and schizophrenia were cross referenced for associations with adipose phenotypes – specifically adipocyte morphology (sample N=895), adipocyte number (sample N=896), spontaneous (sample N=856) and stimulated lipolysis (sample N=875). We used R to carry out linear regression with adjustment for age, sex, population structure and body mass index (BMI; where appropriate). Results: There was no evidence that genetic variation associated with psychiatric disorders (individually or combined in polygenic risk scores) had significant effects on any adipose phenotypes. Conclusions: This study suggests that genetic variation associated with major depressive disorder, bipolar disorder and schizophrenia does not have direct effects on adipocytes.