Genome sequencing broadens the range of contributing variants with clinical implications in schizophrenia

• DOI: 10.1038/s41398-021-01211-2
• Publication Date: 2021-02-01T08:04:32Z
• Authors: Bahareh A. Mojarad; Yue Yin; Roozbeh Manshaei; Ian Backstrom; Gregory Costain; Tracy Heung; Daniele Merico; Christian R. Mars...; Anne S. Bassett; Ryan K. C. Yuen
• Keywords: Indel; Genome-wide Association Study; Clinical Significance

Abstract The range of genetic variation with potential clinical implications in schizophrenia, beyond rare copy number variants (CNVs), remains uncertain. We therefore analyzed genome sequencing data for 259 unrelated adults schizophrenia from a well-characterized community-based cohort previously examined chromosomal microarray CNVs (none 22q11.2 deletions). these genomes high-impact considered causal neurodevelopmental disorders, including single-nucleotide (SNVs) and small insertions/deletions (indels), relevance based on findings disorders. Also, we investigated novel variant type, tandem repeat expansions (TREs), 45 loci known to be associated monogenic neurological diseases. found several this population suggesting that have wider spectrum than thought. In addition pathogenic CNVs, identified 11 (4.3%) individuals clinically relevant SNVs/indels genes converging schizophrenia-relevant pathways. Clinical yield was significantly enriched females those broadly defined learning/intellectual disabilities. Genome analyses also implications, TREs (one DMPK ; two ATXN8OS ) ultra-rare loss-of-function SNVs ZMYM2 (a candidate gene schizophrenia). Of the 233 no (i.e., or implications) 14 (6.0%); some had multiple variants. Mean polygenic risk score similar between without variation; common were not sufficient application. These broaden individual global picture suggest translational value as single technology schizophrenia.