{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T20:39:00Z","timestamp":1779395940701,"version":"3.53.1"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically.<\/jats:p>","DOI":"10.1038\/s41467-019-13380-2","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:04:35Z","timestamp":1575504275000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders"],"prefix":"10.1038","volume":"10","author":[{"given":"L.","family":"D\u2019Abate","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-4968","authenticated-orcid":false,"given":"R. K. C.","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-4697","authenticated-orcid":false,"given":"K.","family":"Tammimies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Buchanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. W.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Thiruvahindrapuram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Brian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. E.","family":"Bryson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Dobkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Howe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Landa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Leef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Messinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ozonoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. L.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z. E.","family":"Warren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Zwaigenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. W.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"key":"13380_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s00787-013-0375-0","volume":"22","author":"T Falkmer","year":"2013","unstructured":"Falkmer, T., Anderson, K., Falkmer, M. & Horlin, C. Diagnostic procedures in autism spectrum disorders: a systematic literature review. Eur. Child Adolesc. Psychiatry 22, 329\u2013340 (2013).","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"13380_CR2","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1542\/peds.2010-2825","volume":"128","author":"S Ozonoff","year":"2011","unstructured":"Ozonoff, S. et al. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics 128, e488\u2013e495 (2011).","journal-title":"Pediatrics"},{"key":"13380_CR3","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1001\/jamapediatrics.2013.2259","volume":"167","author":"TK Gr\u00f8nborg","year":"2013","unstructured":"Gr\u00f8nborg, T. K., Schendel, D. E. & Parner, E. T. Recurrence of autism spectrum disorders in full- and half-siblings and trends over time: a population-based cohort study. JAMA Pediatr. 167, 947\u2013953 (2013).","journal-title":"JAMA Pediatr."},{"key":"13380_CR4","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1176\/appi.ajp.2014.13101359","volume":"171","author":"N Risch","year":"2014","unstructured":"Risch, N. et al. Familial recurrence of autism spectrum disorder: evaluating genetic and environmental contributions. Am. J. Psychiatry 171, 1206\u20131213 (2014).","journal-title":"Am. J. Psychiatry"},{"key":"13380_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-015-0027-y","volume":"6","author":"DS Messinger","year":"2015","unstructured":"Messinger, D. S. et al. Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Mol. Autism 6, 32 (2015).","journal-title":"Mol. Autism"},{"key":"13380_CR6","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/aur.1669","volume":"10","author":"T Charman","year":"2017","unstructured":"Charman, T. et al. Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): a baby siblings research consortium (BSRC) study. Autism Res. J. Int. Soc. Autism Res. 10, 169\u2013178 (2017).","journal-title":"Autism Res. J. Int. Soc. Autism Res."},{"key":"13380_CR7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1001\/jamapsychiatry.2014.3028","volume":"72","author":"E Colvert","year":"2015","unstructured":"Colvert, E. et al. Heritability of autism spectrum disorder in a UK population-based twin sample. JAMA Psychiatry 72, 415\u2013423 (2015).","journal-title":"JAMA Psychiatry"},{"issue":"10","key":"13380_CR8","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1001\/jamapsychiatry.2019.1411","volume":"76","author":"Dan Bai","year":"2019","unstructured":"Bai, D. et al. Association of genetic and environmental factors with autism in a 5-country cohort. JAMA Psychiatry (2019). https:\/\/doi.org\/10.1001\/jamapsychiatry.2019.1411.","journal-title":"JAMA Psychiatry"},{"key":"13380_CR9","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1001\/jama.2014.4144","volume":"311","author":"S Sandin","year":"2014","unstructured":"Sandin, S. et al. The familial risk of autism. JAMA 311, 1770\u20131777 (2014).","journal-title":"JAMA"},{"key":"13380_CR10","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nm.3792","volume":"21","author":"RKC Yuen","year":"2015","unstructured":"Yuen, R. K. C. et al. Whole-genome sequencing of quartet families with autism spectrum disorder. Nat. Med. 21, 185\u2013191 (2015).","journal-title":"Nat. Med."},{"key":"13380_CR11","doi-asserted-by":"publisher","first-page":"7073","DOI":"10.1073\/pnas.1700439114","volume":"114","author":"K Ye","year":"2017","unstructured":"Ye, K. et al. Measuring shared variants in cohorts of discordant siblings with applications to autism. Proc. Natl Acad. Sci. U.S.A. 114, 7073\u20137076 (2017).","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"13380_CR12","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1056\/NEJMoa075974","volume":"358","author":"LA Weiss","year":"2008","unstructured":"Weiss, L. A. et al. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358, 667\u2013675 (2008).","journal-title":"N. Engl. J. Med."},{"key":"13380_CR13","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/ng.3863","volume":"49","author":"DJ Weiner","year":"2017","unstructured":"Weiner, D. J. et al. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nat. Genet. 49, 978\u2013985 (2017).","journal-title":"Nat. Genet."},{"key":"13380_CR14","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1001\/jama.2015.10078","volume":"314","author":"K Tammimies","year":"2015","unstructured":"Tammimies, K. et al. Molecular diagnostic yield of chromosomal microarray analysis and whole-exome sequencing in children with autism spectrum disorder. JAMA 314, 895\u2013903 (2015).","journal-title":"JAMA"},{"key":"13380_CR15","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1126\/science.1138659","volume":"316","author":"J Sebat","year":"2007","unstructured":"Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445\u2013449 (2007).","journal-title":"Science"},{"key":"13380_CR16","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.neuron.2011.05.002","volume":"70","author":"SJ Sanders","year":"2011","unstructured":"Sanders, S. J. et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70, 863\u2013885 (2011).","journal-title":"Neuron"},{"key":"13380_CR17","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/nn.4524","volume":"20","author":"RK C Yuen","year":"2017","unstructured":"C Yuen, R. K. et al. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat. Neurosci. 20, 602\u2013611 (2017).","journal-title":"Nat. Neurosci."},{"key":"13380_CR18","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.ajhg.2014.03.018","volume":"94","author":"D Pinto","year":"2014","unstructured":"Pinto, D. et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am. J. Hum. Genet. 94, 677\u2013694 (2014).","journal-title":"Am. J. Hum. Genet."},{"key":"13380_CR19","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.ajhg.2007.12.009","volume":"82","author":"CR Marshall","year":"2008","unstructured":"Marshall, C. R. et al. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82, 477\u2013488 (2008).","journal-title":"Am. J. Hum. Genet."},{"key":"13380_CR20","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1016\/j.neuron.2011.05.015","volume":"70","author":"D Levy","year":"2011","unstructured":"Levy, D. et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70, 886\u2013897 (2011).","journal-title":"Neuron"},{"key":"13380_CR21","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.ajhg.2016.06.036","volume":"99","author":"VM Leppa","year":"2016","unstructured":"Leppa, V. M. et al. Rare inherited and de novo CNVs reveal complex contributions to ASD risk in multiplex families. Am. J. Hum. Genet. 99, 540\u2013554 (2016).","journal-title":"Am. J. Hum. Genet."},{"key":"13380_CR22","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","volume":"86","author":"DT Miller","year":"2010","unstructured":"Miller, D. T. et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am. J. Hum. Genet. 86, 749\u2013764 (2010).","journal-title":"Am. J. Hum. Genet."},{"issue":"Suppl 1","key":"13380_CR23","doi-asserted-by":"publisher","first-page":"S60","DOI":"10.1542\/peds.2014-3667E","volume":"136","author":"L Zwaigenbaum","year":"2015","unstructured":"Zwaigenbaum, L. et al. Early intervention for children with autism spectrum disorder under 3 years of age: recommendations for practice and research. Pediatrics 136(Suppl 1), S60\u2013S81 (2015).","journal-title":"Pediatrics"},{"key":"13380_CR24","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jaac.2012.12.011","volume":"52","author":"D Messinger","year":"2013","unstructured":"Messinger, D. et al. Beyond autism: a baby siblings research consortium study of high-risk children at three years of age. J. Am. Acad. Child Adolesc. Psychiatry 52, 300\u2013308.e1 (2013).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"13380_CR25","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/jhg.2011.42","volume":"56","author":"A Ramalingam","year":"2011","unstructured":"Ramalingam, A. et al. 16p13.11 duplication is a risk factor for a wide spectrum of neuropsychiatric disorders. J. Hum. Genet. 56, 541\u2013544 (2011).","journal-title":"J. Hum. Genet."},{"key":"13380_CR26","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.biopsych.2014.04.021","volume":"77","author":"E Hanson","year":"2015","unstructured":"Hanson, E. et al. The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population. Biol. Psychiatry 77, 785\u2013793 (2015).","journal-title":"Biol. Psychiatry"},{"key":"13380_CR27","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/978-1-61779-507-7_5","volume":"838","author":"CR Marshall","year":"2012","unstructured":"Marshall, C. R. & Scherer, S. W. Detection and characterization of copy number variation in autism spectrum disorder. Methods Mol. Biol. Clifton NJ 838, 115\u2013135 (2012).","journal-title":"Methods Mol. Biol. Clifton NJ"},{"key":"13380_CR28","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nature12818","volume":"505","author":"H Stefansson","year":"2014","unstructured":"Stefansson, H. et al. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 505, 361\u2013366 (2014).","journal-title":"Nature"},{"key":"13380_CR29","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1001\/jama.2015.4845","volume":"313","author":"K M\u00e4nnik","year":"2015","unstructured":"M\u00e4nnik, K. et al. Copy number variations and cognitive phenotypes in unselected populations. JAMA 313, 2044\u20132054 (2015).","journal-title":"JAMA"},{"key":"13380_CR30","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.biopsych.2016.08.014","volume":"82","author":"KM Kendall","year":"2017","unstructured":"Kendall, K. M. et al. Cognitive performance among carriers of pathogenic copy number variants: analysis of 152,000 UK biobank subjects. Biol. Psychiatry 82, 103\u2013110 (2017).","journal-title":"Biol. Psychiatry"},{"key":"13380_CR31","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1192\/bjp.2018.301","volume":"214","author":"KM Kendall","year":"2019","unstructured":"Kendall, K. M. et al. Cognitive performance and functional outcomes of carriers of pathogenic copy number variants: analysis of the UK Biobank. Br. J. Psychiatry J. Ment. Sci. 214, 297\u2013304 (2019).","journal-title":"Br. J. Psychiatry J. Ment. Sci."},{"key":"13380_CR32","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/mp.2009.101","volume":"16","author":"A Ingason","year":"2011","unstructured":"Ingason, A. et al. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol. Psychiatry 16, 17\u201325 (2011).","journal-title":"Mol. Psychiatry"},{"key":"13380_CR33","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.neuron.2010.10.006","volume":"68","author":"GD Fischbach","year":"2010","unstructured":"Fischbach, G. D. & Lord, C. The Simons Simplex Collection: a resource for identification of autism genetic risk factors. Neuron 68, 192\u2013195 (2010).","journal-title":"Neuron"},{"key":"13380_CR34","unstructured":"Constantino, J. N. & Gruber, C. P. Social Responsiveness Scale: Manual.\u00a0Los Angeles, CA: Western Psychological Services (2005)."},{"key":"13380_CR35","unstructured":"Achenback, T. M. in The Use of Psychological Testing for Treatment Planning and Outcomes Assessment. (ed. Maruish, M. E.) 429\u2013466 (Lawrence Erlbaum Associates Publishers, 1999)."},{"key":"13380_CR36","unstructured":"Sparrow, S. S. et al. Vineland adaptive behavior scales. Circle Pines, MN: American Guidance Service Inc (1984)."},{"key":"13380_CR37","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/s41588-019-0344-8","volume":"51","author":"Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium.","year":"2019","unstructured":"Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431\u2013444 (2019).","journal-title":"Nat. Genet."},{"key":"13380_CR38","doi-asserted-by":"publisher","first-page":"e17","DOI":"10.1542\/peds.2009-0958","volume":"125","author":"G Dawson","year":"2010","unstructured":"Dawson, G. et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics 125, e17\u2013e23 (2010).","journal-title":"Pediatrics"},{"key":"13380_CR39","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1007\/s10803-014-2202-y","volume":"44","author":"SJ Rogers","year":"2014","unstructured":"Rogers, S. J. et al. Autism treatment in the first year of life: a pilot study of infant start, a parent-implemented intervention for symptomatic infants. J. Autism Dev. Disord. 44, 2981\u20132995 (2014).","journal-title":"J. Autism Dev. Disord."},{"issue":"9","key":"13380_CR40","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/S2352-4642(19)30234-2","volume":"3","author":"Connie Kasari","year":"2019","unstructured":"Kasari, C. Time to rethink pre-emptive interventions for infants with early signs of autism spectrum disorder. Lancet Child Adolesc. Health (2019). https:\/\/doi.org\/10.1016\/S2352-4642(19)30234-2.","journal-title":"The Lancet Child & Adolescent Health"},{"issue":"9","key":"13380_CR41","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/S2352-4642(19)30184-1","volume":"3","author":"Andrew J O Whitehouse","year":"2019","unstructured":"Whitehouse, A. J. O. et al. Pre-emptive intervention versus treatment as usual for infants showing early behavioural risk signs of autism spectrum disorder: a single-blind, randomised controlled trial. Lancet Child Adolesc. Health (2019). https:\/\/doi.org\/10.1016\/S2352-4642(19)30184-1.","journal-title":"The Lancet Child & Adolescent Health"},{"key":"13380_CR42","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.jaac.2018.06.022","volume":"57","author":"S Ozonoff","year":"2018","unstructured":"Ozonoff, S. et al. Diagnosis of autism spectrum disorder after age 5 in children evaluated longitudinally since infancy. J. Am. Acad. Child Adolesc. Psychiatry 57, 849\u2013857.e2 (2018).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"13380_CR43","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1002\/aur.1572","volume":"9","author":"M Miller","year":"2016","unstructured":"Miller, M. et al. School-age outcomes of infants at risk for autism spectrum disorder. Autism Res. J. Int. Soc. Autism Res. 9, 632\u2013642 (2016).","journal-title":"Autism Res. J. Int. Soc. Autism Res."},{"key":"13380_CR44","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1177\/1362361315614979","volume":"20","author":"J Brian","year":"2016","unstructured":"Brian, J. et al. Stability and change in autism spectrum disorder diagnosis from age 3 to middle childhood in a high-risk sibling cohort. Autism Int. J. Res. Pract. 20, 888\u2013892 (2016).","journal-title":"Autism Int. J. Res. Pract."},{"key":"13380_CR45","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1002\/aur.1733","volume":"10","author":"E Shephard","year":"2017","unstructured":"Shephard, E. et al. Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder. Autism Res. J. Int. Soc. Autism Res. 10, 546\u2013557 (2017).","journal-title":"Autism Res. J. Int. Soc. Autism Res."},{"key":"13380_CR46","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.biopsych.2013.07.022","volume":"75","author":"G Kirov","year":"2014","unstructured":"Kirov, G. et al. The penetrance of copy number variations for schizophrenia and developmental delay. Biol. Psychiatry 75, 378\u2013385 (2014).","journal-title":"Biol. Psychiatry"},{"key":"13380_CR47","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/ng.3789","volume":"49","author":"JA Kosmicki","year":"2017","unstructured":"Kosmicki, J. A. et al. Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples. Nat. Genet. 49, 504\u2013510 (2017).","journal-title":"Nat. Genet."},{"key":"13380_CR48","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/nature21369","volume":"542","author":"HC Hazlett","year":"2017","unstructured":"Hazlett, H. C. et al. Early brain development in infants at high risk for autism spectrum disorder. Nature 542, 348\u2013351 (2017).","journal-title":"Nature"},{"key":"13380_CR49","doi-asserted-by":"publisher","first-page":"k1674","DOI":"10.1136\/bmj.k1674","volume":"361","author":"L Zwaigenbaum","year":"2018","unstructured":"Zwaigenbaum, L. & Penner, M. Autism spectrum disorder: advances in diagnosis and evaluation. BMJ 361, k1674 (2018).","journal-title":"BMJ"},{"key":"13380_CR50","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/ng1985","volume":"39","author":"Autism Genome Project Consortium.","year":"2007","unstructured":"Autism Genome Project Consortium. et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet. 39, 319\u2013328 (2007).","journal-title":"Nat. Genet."},{"key":"13380_CR51","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s10803-008-0674-3","volume":"39","author":"K Gotham","year":"2009","unstructured":"Gotham, K., Pickles, A. & Lord, C. Standardizing ADOS scores for a measure of severity in autism spectrum disorders. J. Autism Dev. Disord. 39, 693\u2013705 (2009).","journal-title":"J. Autism Dev. Disord."},{"key":"13380_CR52","unstructured":"Mullen, E. M. Mullen scales of early learning. Circle Pines, MN: American Guidance Service Inc (1995). (AGS ed.)."},{"key":"13380_CR53","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1007\/s10803-006-0299-3","volume":"37","author":"RSE Hurley","year":"2007","unstructured":"Hurley, R. S. E., Losh, M., Parlier, M., Reznick, J. S. & Piven, J. The broad autism phenotype questionnaire. J. Autism Dev. Disord. 37, 1679\u20131690 (2007).","journal-title":"J. Autism Dev. Disord."},{"key":"13380_CR54","first-page":"172","volume":"20","author":"M Zarrei","year":"2018","unstructured":"Zarrei, M. et al. De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy. Genet. Med. J. Am. Coll. Med. Genet. 20, 172\u2013180 (2018).","journal-title":"Genet. Med. J. Am. Coll. Med. Genet."},{"key":"13380_CR55","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559\u2013575 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"13380_CR56","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nbt.1852","volume":"29","author":"D Pinto","year":"2011","unstructured":"Pinto, D. et al. Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants. Nat. Biotechnol. 29, 512\u2013520 (2011).","journal-title":"Nat. Biotechnol."},{"key":"13380_CR57","first-page":"Unit 4.14.1","volume":"Chapter 4","author":"K Darvishi","year":"2010","unstructured":"Darvishi, K. Application of Nexus copy number software for CNV detection and analysis. Curr. Protoc. Hum. Genet. Chapter 4, Unit 4.14.1\u201328 (2010).","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"13380_CR58","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/S0076-6879(06)11013-7","volume":"411","author":"T Downey","year":"2006","unstructured":"Downey, T. Analysis of a multifactor microarray study using Partek genomics solution. Methods Enzymol. 411, 256\u2013270 (2006).","journal-title":"Methods Enzymol."},{"key":"13380_CR59","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/nrg3871","volume":"16","author":"M Zarrei","year":"2015","unstructured":"Zarrei, M., MacDonald, J. R., Merico, D. & Scherer, S. W. A copy number variation map of the human genome. Nat. Rev. Genet. 16, 172\u2013183 (2015).","journal-title":"Nat. Rev. Genet."},{"key":"13380_CR60","first-page":"747","volume":"17","author":"M Uddin","year":"2015","unstructured":"Uddin, M. et al. A high-resolution copy-number variation resource for clinical and population genetics. Genet. Med. J. Am. Coll. Med. Genet. 17, 747\u2013752 (2015).","journal-title":"Genet. Med. J. Am. Coll. Med. Genet."},{"key":"13380_CR61","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1176\/appi.ajp.2008.07111711","volume":"165","author":"LJ Bierut","year":"2008","unstructured":"Bierut, L. J. et al. Variants in nicotinic receptors and risk for nicotine dependence. Am. J. Psychiatry 165, 1163\u20131171 (2008).","journal-title":"Am. J. Psychiatry"},{"key":"13380_CR62","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/ng.2554","volume":"45","author":"VJM Verhoeven","year":"2013","unstructured":"Verhoeven, V. J. M. et al. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nat. Genet. 45, 314\u2013318 (2013).","journal-title":"Nat. Genet."},{"key":"13380_CR63","doi-asserted-by":"publisher","first-page":"5082","DOI":"10.1073\/pnas.0911109107","volume":"107","author":"LJ Bierut","year":"2010","unstructured":"Bierut, L. J. et al. A genome-wide association study of alcohol dependence. Proc. Natl. Acad. Sci. U.S.A. 107, 5082\u20135087 (2010).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"13380_CR64","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1158\/1055-9965.EPI-10-0675","volume":"20","author":"JC Figueiredo","year":"2011","unstructured":"Figueiredo, J. C. et al. Genotype-environment interactions in microsatellite stable\/microsatellite instability-low colorectal cancer: results from a genome-wide association study. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol. 20, 758\u2013766 (2011).","journal-title":"Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol."},{"key":"13380_CR65","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1158\/1055-9965.EPI-07-0648","volume":"16","author":"PA Newcomb","year":"2007","unstructured":"Newcomb, P. A. et al. Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol. 16, 2331\u20132343 (2007).","journal-title":"Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol."},{"key":"13380_CR66","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/gerona\/61.10.1059","volume":"61","author":"BH Goodpaster","year":"2006","unstructured":"Goodpaster, B. H. et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J. Gerontol. A. Biol. Sci. Med. Sci. 61, 1059\u20131064 (2006).","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci."},{"key":"13380_CR67","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1016\/j.jacc.2008.12.051","volume":"53","author":"AFR Stewart","year":"2009","unstructured":"Stewart, A. F. R. et al. Kinesin family member 6 variant Trp719Arg does not associate with angiographically defined coronary artery disease in the Ottawa Heart Genomics Study. J. Am. Coll. Cardiol. 53, 1471\u20131472 (2009).","journal-title":"J. Am. Coll. Cardiol."},{"key":"13380_CR68","first-page":"55","volume":"9","author":"M Krawczak","year":"2006","unstructured":"Krawczak, M. et al. PopGen: population-based recruitment of patients and controls for the analysis of complex genotype-phenotype relationships. Community Genet. 9, 55\u201361 (2006).","journal-title":"Community Genet."},{"key":"13380_CR69","first-page":"680","volume":"13","author":"HM Kearney","year":"2011","unstructured":"Kearney, H. M. et al. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet. Med. J. Am. Coll. Med. Genet. 13, 680\u2013685 (2011).","journal-title":"Genet. Med. J. Am. Coll. Med. Genet."},{"key":"13380_CR70","doi-asserted-by":"publisher","first-page":"160271","DOI":"10.1038\/npjgenmed.2016.27","volume":"1","author":"RKC Yuen","year":"2016","unstructured":"Yuen, R. K. C. et al. Genome-wide characteristics of de novo mutations in autism. NPJ Genom. Med. 1, 160271\u20131602710 (2016).","journal-title":"NPJ Genom. Med."},{"key":"13380_CR71","doi-asserted-by":"publisher","unstructured":"Ross, P. J. et al. Synaptic dysfunction in human neurons with autism-associated deletions in PTCHD1-AS. Biol. Psychiatry S0006322319315471 (2019). https:\/\/doi.org\/10.1016\/j.biopsych.2019.07.014.","DOI":"10.1016\/j.biopsych.2019.07.014"},{"key":"13380_CR72","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.ajhg.2011.09.011","volume":"89","author":"ME Talkowski","year":"2011","unstructured":"Talkowski, M. E. et al. Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder. Am. J. Hum. Genet. 89, 551\u2013563 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"13380_CR73","unstructured":"Team, R. C. R: A language and environment for statistical computing. (Team, R. C, 2013)."},{"key":"13380_CR74","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/ng1416","volume":"36","author":"AJ Iafrate","year":"2004","unstructured":"Iafrate, A. J. et al. Detection of large-scale variation in the human genome. Nat. Genet. 36, 949\u2013951 (2004).","journal-title":"Nat. Genet."},{"key":"13380_CR75","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1101\/gr.6861907","volume":"17","author":"K Wang","year":"2007","unstructured":"Wang, K. et al. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res. 17, 1665\u20131674 (2007).","journal-title":"Genome Res."},{"key":"13380_CR76","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1093\/nar\/gkm076","volume":"35","author":"S Colella","year":"2007","unstructured":"Colella, S. et al. QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucl. Acids Res. 35, 2013\u20132025 (2007).","journal-title":"Nucl. Acids Res."},{"key":"13380_CR77","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1093\/bioinformatics\/btu848","volume":"31","author":"J Euesden","year":"2015","unstructured":"Euesden, J., Lewis, C. M. & O\u2019Reilly, P. F. PRSice: polygenic risk score software. Bioinforma. Oxf. Engl. 31, 1466\u20131468 (2015).","journal-title":"Bioinforma. Oxf. Engl."},{"key":"13380_CR78","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/s41588-019-0344-8","volume":"51","author":"J Grove","year":"2019","unstructured":"Grove, J. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431\u2013444 (2019).","journal-title":"Nat. Genet."},{"key":"13380_CR79","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1038\/ng.3039","volume":"46","author":"T Gaugler","year":"2014","unstructured":"Gaugler, T. et al. Most genetic risk for autism resides with common variation. Nat. Genet. 46, 881\u2013885 (2014).","journal-title":"Nat. Genet."},{"key":"13380_CR80","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1001\/jama.2017.12141","volume":"318","author":"S Sandin","year":"2017","unstructured":"Sandin, S. et al. The heritability of autism spectrum disorder. JAMA 318, 1182\u20131184 (2017).","journal-title":"JAMA"},{"key":"13380_CR81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/DBP.0000000000000235","volume":"37","author":"DL Christensen","year":"2016","unstructured":"Christensen, D. L. et al. Prevalence and characteristics of autism spectrum disorder among 4-year-old children in the autism and developmental disabilities monitoring network. J. Dev. Behav. Pediatr. JDBP 37, 1\u20138 (2016).","journal-title":"J. Dev. Behav. Pediatr. JDBP"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-13380-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-13380-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-13380-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T02:20:27Z","timestamp":1671243627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-019-13380-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,5]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["13380"],"URL":"https:\/\/doi.org\/10.1038\/s41467-019-13380-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,5]]},"assertion":[{"value":"30 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.W.S. is on Scientific Advisory Committees for Population Bio and Deep Genomics, and his institution, The Hospital for Sick Children, has licensed to Lineagen software code he co-developed: \u201cMethod of determining disease causality of genome mutations\u201d.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5519"}}