In:
Nature Genetics, Springer Science and Business Media LLC, Vol. 54, No. 9 ( 2022-09), p. 1305-1319
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.
Type of Medium:
Online Resource
ISSN:
1061-4036
,
1546-1718
DOI:
10.1038/s41588-022-01148-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
1494946-5
SSG:
12
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