Shared Genetic Predispositions to Delusions and Hallucinations in Substance Use Disorders and Bipolar Disorder

Delusions and hallucinations can be seen in a subgroup of patients who abuse substance like methamphetamine or alcohol as well as in a subgroup of those with bipolar disorder. Substance-induced psychosis and bipolar disorder are both severe psychiatric disorders with substantial phenotypic and genetic complexity. Psychotic features, including delusions and hallucinations, frequently occur in bipolar disorder during manic and depressive episodes, and may be indicative of a more homogeneous, genetically meaningful subtype of the disorder. We hypothesize that shared genetic predispositions to delusions and hallucinations in substance use disorders and bipolar disorder can be precipitated by substance use or affective episodes, and that specific susceptibility genes for delusions and hallucinations in bipolar disorder can be replicated among patients with substance-induced psychotic disorder.Our preliminary genome-wide association study (GWAS) analyses have identified two single nucleotide polymorphisms (SNPs) located between human glypican 5 (GPC5) and glypican 6 (GPC6) genes showing significant association with auditory hallucinations, with significant replication. One of these two SNPs has a p-value of 1.4 x 10-5 in the first GWAS and a p-value of 0.007 in the replication study. The p-value in joint analysis is 9.4 x 10-8.In this project, we aim to recruit 500 patients with substance-induced psychotic disorder, and 500 patients with substance use disorder without experience of psychosis as controls, matched in types of substance. The top SNPs associated with delusions or hallucinations in bipolar disorder patients GWAS analyses are to be replicated in these subjects. Deep sequencing will be performed for selected candidate genes to find causative functional polymorphisms of delusions and hallucinations. We expect to identify susceptibility genes for delusions and hallucinations in both bipolar disorder and substance use disorder, and to determine functions of these genes in the future.

Project ID:PC10708-1060
External Project ID:MOST107-2314-B182-065