@article{a60be68c3a2a463cafddf607a56ca11b,
title = "Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes",
abstract = "To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10−6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect. Autistic individuals with LoF variants in the four moderate-risk genes (NAV3, ITSN1, SCAF1 and HNRNPUL2; n = 95) have less cognitive impairment than 129 autistic individuals with LoF variants in highly penetrant genes (CHD8, SCN2A, ADNP, FOXP1 and SHANK3) (59% vs 88%, P = 1.9 × 10−6). Power calculations suggest that much larger numbers of autism cases are needed to identify additional moderate-risk genes.",
author = "{The SPARK Consortium} and Xueya Zhou and Pamela Feliciano and Chang Shu and Tianyun Wang and Irina Astrovskaya and Hall, {Jacob B.} and Obiajulu, {Joseph U.} and Wright, {Jessica R.} and Murali, {Shwetha C.} and Xu, {Simon Xuming} and Leo Brueggeman and Thomas, {Taylor R.} and Olena Marchenko and Christopher Fleisch and Barns, {Sarah D.} and Snyder, {Lee Anne Green} and Bing Han and Chang, {Timothy S.} and Turner, {Tychele N.} and Harvey, {William T.} and Andrew Nishida and O{\textquoteright}Roak, {Brian J.} and Geschwind, {Daniel H.} and Adrienne Adams and Alpha Amatya and Alicia Andrus and Asif Bashar and Anna Berman and Alison Brown and Alexies Camba and Gulsrud, {Amanda C.} and Krentz, {Anthony D.} and Shocklee, {Amanda D.} and Amy Esler and Lash, {Alex E.} and Anne Fanta and Ali Fatemi and Angela Fish and Alexandra Goler and Antonio Gonzalez and Anibal Gutierrez and Antonio Hardan and Amy Hess and Anna Hirshman and Alison Holbrook and Ace, {Andrea J.} and Griswold, {Anthony J.} and Wodka, {Ericka L.} and Law, {J. Kiely} and Landa, {Rebecca J.}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = sep,
doi = "10.1038/s41588-022-01148-2",
language = "English (US)",
volume = "54",
pages = "1305--1319",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "9",
}