RT Journal Article SR Electronic T1 Paternally inherited noncoding structural variants contribute to autism JF bioRxiv FD Cold Spring Harbor Laboratory SP 102327 DO 10.1101/102327 A1 William M Brandler A1 Antaki Danny A1 Madhusudan Gujral A1 Morgan L Kleiber A1 Michelle S Maile A1 Oanh Hong A1 Timothy R Chapman A1 Shirley Tan A1 Prateek Tandon A1 Timothy Pang A1 Shih C Tang A1 Keith K Vaux A1 Yan Yang A1 Eoghan Harrington A1 Sissel Juul A1 Daniel J Turner A1 Stephen F Kingsmore A1 Joseph G Gleeson A1 Boyko Kakaradov A1 Amalio Telenti A1 J Craig Venter A1 Roser Corominas A1 Bru Cormand A1 Isabel Rueda A1 Karen S Messer A1 Caroline M Nievergelt A1 Maria J Arranz A1 Eric Courchesne A1 Karen Pierce A1 Alysson R Muotri A1 Lilia M Iakoucheva A1 Amaia Hervas A1 Christina Corsello A1 Jonathan Sebat YR 2017 UL http://biorxiv.org/content/early/2017/03/29/102327.abstract AB The genetic architecture of autism spectrum disorder (ASD) is known to consist of contributions from gene-disrupting de novo mutations and common variants of modest effect. We hypothesize that the unexplained heritability of ASD also includes rare inherited variants with intermediate effects. We investigated the genome-wide distribution and functional impact of structural variants (SVs) through whole genome analysis (≥30X coverage) of 3,169 subjects from 829 families affected by ASD. Genes that are intolerant to inactivating variants in the exome aggregation consortium (ExAC) were depleted for SVs in parents, specifically within fetal-brain promoters, UTRs and exons. Rare paternally-inherited SVs that disrupt promoters or UTRs were over-transmitted to probands (P = 0.0013) and not to their typically-developing siblings. Recurrent functional noncoding deletions implicate the gene LEO1 in ASD. Protein-coding SVs were also associated with ASD (P = 0.0025). Our results establish that rare inherited SVs predispose children to ASD, with differing contributions from each parent.