GWAS SNPs Impact Shared Regulatory Pathways Amongst Multimorbid Psychiatric Disorders and Cognitive Functioning
Year: 2020
Type: article
Abstract: The regulatory contribution that single-nucleotide polymorphisms (SNPs) associated with psychiatric and cognitive phenotypes make to multimorbidity is unknown. Here, we integrate 3D genome organization and expression quantitative trait (eQTL) analyses to identify the genes and biological pathways that are functionally impacted by 2,893 GWAS SNPs associated with cognitive functioning and five psychiatric disorders (i.e. attention deficit hyperactivity disorder (ADHD), anxiety, bipolar disorder (BD), unipolar depression (UD) and schizophrenia (SCZ)). The analysis revealed 33 genes and 62 pathways that were commonly affected by the gene regulatory interactions associated with all six phenotypes despite there being no common SNPs and eQTLs. 38 ADHD-, 78 anxiety-, 81 BD-, 169 UD-, 225 SCZ- and 185 cognition-associated genes represent known drug targets. Four genes were affected by eQTLs from all six phenotypes. Collectively, our results represent the foundation for a shift from a gene-targeted towards a pathway-based approach to the treatment of multimorbid conditions.
Source: Frontiers in Psychiatry
Institution: University of Auckland
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Royal Society Te Apārangi, National Institutes of Health, Marsden Fund, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Common Fund
OpenAlex ID: W3093916766