@article{96376d1fed3946e7a07cebf6a041d313,
title = "Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder",
abstract = "Whole-genome sequencing (WGS) has facilitated the first genome-wide evaluations of the contribution of de novo noncoding mutations to complex disorders. Using WGS, we identified 255,106 de novo mutations among sample genomes from members of 1902 quartet families in which one child, but not a sibling or their parents, was affected by autism spectrum disorder (ASD). In contrast to coding mutations, no noncoding functional annotation category, analyzed in isolation, was significantly associated with ASD. Casting noncoding variation in the context of a de novo risk score across multiple annotation categories, however, did demonstrate association with mutations localized to promoter regions. We found that the strongest driver of this promoter signal emanates from evolutionarily conserved transcription factor binding sites distal to the transcription start site. These data suggest that de novo mutations in promoter regions, characterized by evolutionary and functional signatures, contribute to ASD.",
author = "An, {Joon Yong} and Kevin Lin and Lingxue Zhu and Werling, {Donna M.} and Shan Dong and Harrison Brand and Wang, {Harold Z.} and Xuefang Zhao and Schwartz, {Grace B.} and Collins, {Ryan L.} and Currall, {Benjamin B.} and Claudia Dastmalchi and Jeanselle Dea and Clif Duhn and Gilson, {Michael C.} and Lambertus Klei and Lindsay Liang and Eirene Markenscoff-Papadimitriou and Sirisha Pochareddy and Nadav Ahituv and Buxbaum, {Joseph D.} and Hilary Coon and Daly, {Mark J.} and Kim, {Young Shin} and Marth, {Gabor T.} and Neale, {Benjamin M.} and Quinlan, {Aaron R.} and Rubenstein, {John L.} and Nenad Sestan and State, {Matthew W.} and Willsey, {A. Jeremy} and Talkowski, {Michael E.} and Bernie Devlin and Kathryn Roeder and Sanders, {Stephan J.}",
note = "Publisher Copyright: {\textcopyright} 2018 American Association for the Advancement of Science. All rights reserved.",
year = "2018",
month = dec,
day = "14",
doi = "10.1126/science.aat6576",
language = "English",
volume = "362",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6420",
}