Authors
Daniel P Howrigan, Samuel A Rose, Kaitlin E Samocha, Menachem Fromer, Felecia Cerrato, Wei J Chen, Claire Churchhouse, Kimberly Chambert, Sharon D Chandler, Mark J Daly, Ashley Dumont, Giulio Genovese, Hai-Gwo Hwu, Nan Laird, Jack A Kosmicki, Jennifer L Moran, Cheryl Roe, Tarjinder Singh, Shi-Heng Wang, Stephen V Faraone, Stephen J Glatt, Steven A McCarroll, Ming Tsuang, Benjamin M Neale
Publication date
2020/2
Journal
Nature neuroscience
Volume
23
Issue
2
Pages
185-193
Publisher
Nature Publishing Group US
Description
Protein-coding de novo mutations (DNMs) are significant risk factors in many neurodevelopmental disorders, whereas schizophrenia (SCZ) risk associated with DNMs has thus far been shown to be modest. We analyzed DNMs from 1,695 SCZ-affected trios and 1,077 published SCZ-affected trios to better understand the contribution to SCZ risk. Among 2,772 SCZ probands, exome-wide DNM burden remained modest. Gene set analyses revealed that SCZ DNMs were significantly concentrated in genes that were highly expressed in the brain, that were under strong evolutionary constraint and/or overlapped with genes identified in other neurodevelopmental disorders. No single gene surpassed exome-wide significance; however, 16 genes were recurrently hit by protein-truncating DNMs, corresponding to a 3.15-fold higher rate than the mutation model expectation (permuted 95% confidence interval: 1–10 genes …
Scholar articles
DP Howrigan, SA Rose, KE Samocha, M Fromer… - Nature neuroscience, 2020