作者
Tianyun Wang, Kendra Hoekzema, Davide Vecchio, Huidan Wu, Arvis Sulovari, Bradley P Coe, Madelyn A Gillentine, Amy B Wilfert, Luis A Perez-Jurado, Malin Kvarnung, Yoeri Sleyp, Rachel K Earl, Jill A Rosenfeld, Madeleine R Geisheker, Lin Han, Bing Du, Chris Barnett, Elizabeth Thompson, Marie Shaw, Renee Carroll, Kathryn Friend, Rachael Catford, Elizabeth E Palmer, Xiaobing Zou, Jianjun Ou, Honghui Li, Hui Guo, Jennifer Gerdts, Emanuela Avola, Giuseppe Calabrese, Maurizio Elia, Donatella Greco, Anna Lindstrand, Ann Nordgren, Britt-Marie Anderlid, Geert Vandeweyer, Anke Van Dijck, Nathalie Van der Aa, Brooke McKenna, Miroslava Hancarova, Sarka Bendova, Marketa Havlovicova, Giovanni Malerba, Bernardo Dalla Bernardina, Pierandrea Muglia, Arie van Haeringen, Mariette JV Hoffer, Barbara Franke, Gerarda Cappuccio, Martin Delatycki, Paul J Lockhart, Melanie A Manning, Pengfei Liu, Ingrid E Scheffer, Nicola Brunetti-Pierri, Nanda Rommelse, David G Amaral, Gijs WE Santen, Elisabetta Trabetti, Zdeněk Sedláček, Jacob J Michaelson, Karen Pierce, Eric Courchesne, R Frank Kooy, Magnus Nordenskjöld, Corrado Romano, Hilde Peeters, Raphael A Bernier, Jozef Gecz, Kun Xia, Evan E Eichler
发表日期
2020/10/1
期刊
Nature communications
卷号
11
期号
1
页码范围
4932
出版商
Nature Publishing Group UK
简介
Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E−06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER …
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