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Quantitative trait locus analysis of nonverbal communication in autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental syndrome marked by impairments in social interactive functioning and communication skills, and the presence of repetitive and restrictive behaviors. Twin and linkage studies provide evidence that ASD is heritable and genetically complex. Genetic analyses of familial quantitative traits in those with ASD may help to reveal underlying risk genes. We report a quantitative trait locus (QTL) analysis of nonverbal communication (NVC) in 228 families from the autism genetics resource exchange (AGRE) ascertained for at least two siblings with ASD. QTL at 1p13–q12, 4q21–25, 7q35, 8q23–24, and 16p12–13 indicate that genes at these loci may contribute to the variation in NVC among those with ASD. Using the criteria of Lander and Kruglyak, the QTL at 1p13–q12 is ‘suggestive’, while the other four are ‘possible’. To assess whether these QTL are likely to harbor genes contributing specifically to the deficits in NVC, linkage analysis of ASD sibships with the most severe NVC scores was conducted. The sibships were identified by ordered-subset analyses (OSA), and families with the most severe NVC scores displayed lod scores of 3.4 at 8q23–24 and 3.8 at 16p12–13, indicating that these two regions are likely to harbor gene(s) contributing to ASD by predisposing to deficits in NVC.

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Acknowledgements

This work was supported by National Institutes of Health Grants T32 HG02536 (GKC) and MH64547 (DHG, RMC). We thank the AGRE families who participated in this study, the Cure Autism Now Foundation (CAN) for supporting the AGRE program, and the scientists who have provided oversight to the AGRE consortium. Members of AGRE Consortium are Daniel H Geschwind, University of California at Los Angeles, Los Angeles; Maja Bucan, University of Pennsylvania, Philadelphia; W Ted Brown, New York State Institute for Basic Research in Developmental Disabilities, Staten Island; Joseph D Buxbaum, Mt Sinai School of Medicine, New York; Rita M Cantor, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles; John N Constantino, Washington University School of Medicine, St Louis; T Conrad Gilliam, University of Chicago, Chicago; David H Ledbetter, Emory University, Atlanta; Stanley F Nelson, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles; Gerard D Schellenberg, University of Washington and Veterans Affairs Medical Center, Seattle; Carol A Samango-Sprouse, George Washington University, Washington; and Rudolph E Tanzi, Massachusetts General Hospital, Boston.

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Correspondence to R M Cantor.

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Chen, G., Kono, N., Geschwind, D. et al. Quantitative trait locus analysis of nonverbal communication in autism spectrum disorder. Mol Psychiatry 11, 214–220 (2006). https://doi.org/10.1038/sj.mp.4001753

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