Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 64,998 bioRxiv papers from 288,069 authors.

Protein-coding de novo mutations (DNMs) in the form of single nucleotide changes and short insertions/deletions are significant genetic risk factors for autism, intellectual disability, developmental delay, and epileptic encephalopathy. In contrast, the burden of DNMs has thus far only had a modest documented impact on schizophrenia (SCZ) risk. Here, we analyze whole-exome sequence from 1,695 SCZ affected parent-offspring trios from Taiwan along with DNMs from 1,077 published SCZ trios to better understand the contribution of coding DNMs to SCZ risk. Among 2,772 SCZ affected probands, the increased burden of DNMs is modest. Gene set analyses show that the modest increase in risk from DNMs in SCZ probands is concentrated in genes that are either highly brain expressed, under strong evolutionary constraint, and/or overlap with genes identified as DNM risk factors in other neurodevelopmental disorders. No single gene meets the criteria for genome-wide significance, but we identify 16 genes that are recurrently hit by a protein-truncating DNM, which is a 3.15-fold higher rate than mutation model expectation of 5.1 genes (permuted 95% CI=1-10 genes, permuted p=3e-5). Overall, DNMs explain only a small fraction of SCZ risk, and this risk is polygenic in nature suggesting that coding variation across many different genes will be a risk factor for SCZ in the population.

Download data

  • Downloaded 602 times
  • Download rankings, all-time:
    • Site-wide: 15,818 out of 64,998
    • In genetics: 1,087 out of 3,686
  • Year to date:
    • Site-wide: 8,590 out of 64,998
  • Since beginning of last month:
    • Site-wide: 14,255 out of 64,998

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


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


News