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DOI | 10.1126/science.aat6576 |
Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder | |
An, Joon-Yong1; Lin, Kevin2; Zhu, Lingxue2; Werling, Donna M.1; Dong, Shan1; Brand, Harrison3,4,5,6,7; Wang, Harold Z.3,4; Zhao, Xuefang3,4,5,6,7; Schwartz, Grace B.1; Collins, Ryan L.3,4,5,8; Currall, Benjamin B.3,4,5,6,7; Dastmalchi, Claudia1; Dea, Jeanselle1; Duhn, Clif1; Gilson, Michael C.1; Klei, Lambertus9; Liang, Lindsay1; Markenscoff-Papadimitriou, Eirene1; Pochareddy, Sirisha10,11; Ahituv, Nadav12,13; Buxbaum, Joseph D.14,15,16,17; Coon, Hilary18,19; Daly, Mark J.3,6,7,20,21; Kim, Young Shin1; Marth, Gabor T.22,23; Neale, Benjamin M.3,6,7,20,21; Quinlan, Aaron R.19,22,23; Rubenstein, John L.1; Sestan, Nenad10,11; State, Matthew W.1,13; Willsey, A. Jeremy1,24,25; Talkowski, Michael E.3,4,5,6,7,26,27; Devlin, Bernie9; Roeder, Kathryn2,28; Sanders, Stephan J.1,13 | |
2018-12-14 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6420页码:1270-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000452994400047 |
WOS关键词 | VARIANTS ; MUTATIONS ; ASSOCIATION ; ELEMENTS ; TOOL |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200322 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Psychiat, San Francisco, CA 94143 USA; 2.Carnegie Mellon Univ, Dept Stat & Data Sci, Pittsburgh, PA 15213 USA; 3.Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA; 4.Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA; 5.Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA; 6.Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA; 7.Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA; 8.Harvard Med Sch, Div Med Sci, Program Bioinformat & Integrat Genom, Boston, MA USA; 9.Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA; 10.Yale Sch Med, Dept Neurosci, New Haven, CT 06510 USA; 11.Yale Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA; 12.Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA; 13.Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA; 14.Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA; 15.Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA; 16.Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA; 17.Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA; 18.Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84112 USA; 19.Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA; 20.Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA; 21.Harvard Med Sch, Dept Med, Boston, MA USA; 22.Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA; 23.Univ Utah, Sch Med, USTAR Ctr Genet Discovery, Salt Lake City, UT USA; 24.Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA; 25.Univ Calif San Francisco, Quantitat Biosci Inst, San Francisco, CA 94143 USA; 26.Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA; 27.Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA; 28.Carnegie Mellon Univ, Computat Biol Dept, Pittsburgh, PA 15213 USA |
推荐引用方式 GB/T 7714 | An, Joon-Yong,Lin, Kevin,Zhu, Lingxue,et al. Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder[J]. SCIENCE,2018,362(6420):1270-+. |
APA | An, Joon-Yong.,Lin, Kevin.,Zhu, Lingxue.,Werling, Donna M..,Dong, Shan.,...&Sanders, Stephan J..(2018).Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder.SCIENCE,362(6420),1270-+. |
MLA | An, Joon-Yong,et al."Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder".SCIENCE 362.6420(2018):1270-+. |
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