Many neuropsychiatric disorders have overlapping clinical presentations, suggesting shared genes. Research points to a genetic etiology for 5 major psychiatric disorders: schizophrenia (SCZ), bipolar disorder (BPD), autism spectrum disorders (ASD), ADHD and depression. Do these 5 disorders have shared genes?
Gene-based meta-analysis of 5 study cohorts comprised 7849 cases and 10,799 controls. Cases had SCZ, BPD, AUD, ADHD, and/or depression. Case-control association testing was performed on gene copy number variations (CNVs) from each cohort. Quantitative PCR was used to validate newly identified loci.
Findings suggest significant overlap between genetic risk loci across all 5 disorder cohorts. Two new variants were identified that showed a significant association among all 5 disorders in all 5 cohorts and (meta P value for duplications = 7.5 × 10-7): OCK8: expressed in brain tissue; mutations linked to intellectual disability; KANK1: role in neuronal function; mutations cause cerebral palsy and spastic quadriplegia type 2. Results linked DOCK8/KANK1 with the 5 disorders. Quantitative PCR was used to validate the results.
“The discovery of CNVs in DOCK8 and KANK1 across all 5 diseases not only adds to the growing catalog of neurodevelopmental variants but also paves the way for new diagnostics opportunities and interventions which could be applied across multiple clinical indications,” wrote first author Joseph Glessner, PhD, of Children’s Hospital of Philadelphia, Philadelphia, and the Janssen-CHOP Neuropsychaitric Genomics Working Group.
This first large-scale meta-analysis of shared genes across SCZ, BPD, AUD, ADHD, and/or depression found significant overlap between genetic risk loci across all 5 disease cohorts. The study identified 2 new genetic variants, DOCK8 and KANK1, which were significantly associated with all 5 disorders. These results could be used to develop new diagnostic instruments and treatments for a range of neuropsychiatric disorders.