Polygenic risk for type 2 diabetes mellitus among individuals with psychosis and their relatives

Abstract

Background An elevated prevalence of Type 2 diabetes (T2D) has been observed in people with psychotic disorders and their relatives compared to the general population. It is not known whether this population also has increased genetic risk for T2D. Methods Subjects included probands with schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder, their first-degree relatives without psychotic disorders, and healthy controls, who participated in the Bipolar Schizophrenia Network for Intermediate Phenotypes study. We constructed sets of polygenic risk scores for T2D (PGRST2D) and schizophrenia (PGRSSCHIZ) using publicly available data from genome-wide association studies. We then explored the correlation of PGRST2D with psychiatric proband or relative status, and with self-reported diabetes. Caucasians and African-Americans were analyzed separately. We also evaluated correlations between PGRSSCHIZ and diabetes mellitus among Caucasian probands and their relatives. Results In Caucasians, PGRST2D was correlated with self-reported diabetes mellitus within probands, but was not correlated with proband or relative status in the whole sample. In African-Americans, a PGRST2D based on selected risk alleles for T2D in this population did not correlate with proband or relative status. PGRSSCHIZ was not correlated with self-reported diabetes within Caucasian probands. Conclusion Differences in polygenic risk for T2D do not explain the increased prevalence of diabetes mellitus observed in psychosis probands and their relatives.

Evidence that genes involved in hedgehog signaling are associated with both bipolar disorder and high BMI

“…However, proteins encoded by these genes showed more interactions compared to what would be expected for a random set or proteins of similar size extracted from the genome. The limited number of genetic targets we observed to be shared between BD and T2D is in accordance with previous studies showing a lack of association between T2D polygenic risk scores (PRS) and diagnosis of psychiatric disorders 32,35 . Although the aggregated effect of multiple T2D-associated variants might not play a relevant role in BD pathophysiology, the contribution of specific genes might still be important.…”

Evidence for genetic contribution to the increased risk of type 2 diabetes in schizophrenia

“…To our knowledge, three other studies have to date compared risk scores for T2D and SCZ 36 , 49 , 50 . Purcell et al first performed SCZ risk scores analysis in a T2D sample but did not identify a significant correlation between scores and phenotype 36 , potentially due to the relatively low sample sizes available at the time (~3300 cases for SCZ; ~1900 cases for T2D).…”

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

“…Two meta-analyses provide evidence for impaired glucose tolerance and insulin resistance in those with a first episode of schizophrenia (Perry et al, 2016;Pillinger et al, 2017), and there is also evidence that relatives of patients with schizophrenia have a higher than expected prevalence of diabetes (Mothi et al, 2015). However, analysis of data derived from genome-wide association studies has not provided consistent evidence regarding a possible genetic contribution to the risk of type-2 diabetes in individuals with schizophrenia (Padmanabhan et al, 2016;Hackinger et al, 2018).…”