- Brandler, William M;
- Antaki, Danny;
- Gujral, Madhusudan;
- Kleiber, Morgan L;
- Whitney, Joe;
- Maile, Michelle S;
- Hong, Oanh;
- Chapman, Timothy R;
- Tan, Shirley;
- Tandon, Prateek;
- Pang, Timothy;
- Tang, Shih C;
- Vaux, Keith K;
- Yang, Yan;
- Harrington, Eoghan;
- Juul, Sissel;
- Turner, Daniel J;
- Thiruvahindrapuram, Bhooma;
- Kaur, Gaganjot;
- Wang, Zhuozhi;
- Kingsmore, Stephen F;
- Gleeson, Joseph G;
- Bisson, Denis;
- Kakaradov, Boyko;
- Telenti, Amalio;
- Venter, J Craig;
- Corominas, Roser;
- Toma, Claudio;
- Cormand, Bru;
- Rueda, Isabel;
- Guijarro, Silvina;
- Messer, Karen S;
- Nievergelt, Caroline M;
- Arranz, Maria J;
- Courchesne, Eric;
- Pierce, Karen;
- Muotri, Alysson R;
- Iakoucheva, Lilia M;
- Hervas, Amaia;
- Scherer, Stephen W;
- Corsello, Christina;
- Sebat, Jonathan
The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.