Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 70,230 bioRxiv papers from 306,634 authors.

By meta-analyzing rare coding variants in whole-exome sequences of 4,264 schizophrenia cases and 9,343 controls, de novo mutations in 1,077 trios, and array-based copy number variant calls from 6,882 cases and 11,255 controls, we show that individuals with schizophrenia carry a significant burden of rare damaging variants in a subset of 3,230 "highly constrained" genes previously identified as having near-complete depletion of protein truncating variants. Furthermore, rare variant enrichment analyses demonstrate that this burden is concentrated in known autism spectrum disorder risk genes, genes diagnostic of severe developmental disorders, and the autism-implicated sets of promoter targets of CHD8, and mRNA targets of FMRP. We further show that schizophrenia patients with intellectual disability have a greater enrichment of rare damaging variants in highly constrained genes and developmental disorder genes, but that a weaker but significant enrichment exists throughout the larger schizophrenia population. Combined, our results demonstrate that schizophrenia risk loci of large effect across a range of variant types implicate a common set of genes shared with broader neurodevelopmental disorders, suggesting a path forward in identifying additional risk genes in psychiatric disorders and further supporting a neurodevelopmental etiology to the pathogenesis of schizophrenia.

Download data

  • Downloaded 844 times
  • Download rankings, all-time:
    • Site-wide: 10,739 out of 70,235
    • In genetics: 779 out of 3,897
  • Year to date:
    • Site-wide: 39,645 out of 70,235
  • Since beginning of last month:
    • Site-wide: 56,451 out of 70,235

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News