Mapping autism risk loci using genetic linkage and chromosomal rearrangements

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  • A Corrigendum to this article was published on 01 October 2007


Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12–p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

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Figure 1: Linkage across the genome for all families and ancestries, based on levels of diagnostic certainty.
Figure 2: Chromosome ideogram depicting 253 inferred CNVs found in 196 individuals with ASDs.
Figure 3: Highlighted linkage results due to removing families in which affected individuals carry putative CNVs.
Figure 4: Linkage peaks by male-only versus female-containing families, based on levels of diagnostic certainty.
Figure 5: The effect on linkage of splitting families into female-containing and male-only families while also removing families in which affected individuals putatively carry CNVs.

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Change history

  • 26 September 2007

    In the version of this article initially published, Kacie J. Meyer (University of Iowa, Iowa City) was inadvertently omitted from the author list, and the names of three authors (Frederieke Koop, Marjolein Langemeijer and Channa Hijmans) were misspelled. There were also minor errors in the abstract (“1,168 families” should read “1,181 families”) and in the final paragraph of the Discussion (“11q13–12” should read “11p13–12”). These errors have been corrected in the HTML and PDF versions of the article.


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The authors are indebted to the participating families for their contribution of time and effort in support of this study. We gratefully acknowledge Autism Speaks, formerly the National Alliance for Autism Research, for financial support for data pooling, SNP genotyping and data analysis.

The Autism Genetics Cooperative thanks Assistance Publique-Hôpitaux de Paris, Canadian Institutes for Health Research (CIHR grant 11350 to P.S.), Catherine and Maxwell Meighan Foundation, Fondation de France, Fondation France Télécom, Fondation pour la Recherche Médicale, Genome Canada/Ontario Genomics Institute, The Hospital for Sick Children Foundation, Howard Hughes Medical Institute, INSERM, McLaughlin Centre for Molecular Medicine, National Institute of Child Health and Human Development, National Institute of Mental Health (MH066673 to J.D.B.; MH55135 to S.E.F.; MH52708 to N. Risch (University of California, San Francisco); MH061009 to J.S.S.), National Institute of Neurological Disorders and Stroke (NS042165 to J.H.; NS026630 and NS036738 to M.A.P.-V.; NS049261 to J.S.S.; NS043550 to T.H.W.), Swedish Science Council, Seaver Autism Research Foundation and The Centre for Applied Genomics (Toronto). S.W.S. is an Investigator of the CIHR and an HHMI International Scholar.

The Autism Genetic Resource Exchange Consortium gratefully acknowledges the resources provided by the participating families. The Autism Genetic Resource Exchange is a program of Cure Autism Now and is supported, in part, by the National Institute of Mental Health (MH64547 to D.H.G.).

The Collaborative Programs of Excellence thank the National Center for Research Resources (M01-RR00064), National Institute of Child Health and Human Development (U19HD34565 G.D. and G.S.), NIMH (MH057881), NINDS (5 U19 HD035476 to W.M.McM.) and the Utah Autism Foundation.

The International Molecular Genetic Study of Autism Consortium thanks the UK Medical Research Council, Wellcome Trust, BIOMED 2 (CT-97-2759), EC Fifth Framework (QLG2-CT-1999-0094), Telethon-Italy (GGP030227), Janus Korczak Foundation, Deutsche Forschungsgemeinschaft, Fondation France Telecom, Conseil Regional Midi-Pyrenees, Danish Medical Research Council, Sofiefonden, Beatrice Surovell Haskells Fond for Child Mental Health Research of Copenhagen, Danish Natural Science Research Council (9802210) and the US National Institutes of Health (U19 HD35482, MO1 RR06022, K05 MH01196, K02 MH01389). A.J.B. is the Cheryl and Reece Scott Professor of Psychiatry. A.P.M. is a Wellcome Trust Principal Research Fellow.

Requests for data or methods should be addressed to B.D. ( or S.W.S. (

Author information

P.S., A.D.P., S.W.S., V.J.V., M.A.P.-V., C.B., J.D.B., J.H., J.S.S., J.H., J.L.H., J.P., T.H.W., D.H.G., R.C., S.N., G.D., G.D.S., B.D., W.M.M., E.M.W., A.J.B., A.P.M. and E.H.C. were lead AGP investigators and contributed equally to this project.

The Autism Genome Project (AGP). The AGP comprises four existing consortia of partners or countries (listed alphabetically below).

Autism Genetics Cooperative. Canagen: P.S., A.D.P., L.Z., W.R., J.B., X.-Q.L., J.B.V., J.L.S., A.P.T., L.S., L.F., C.Q., S.E.B., M.B.J., C.R.M. and S.W.S. Iowa Data Coordinating Center: V.J.V., C.B., L.V.M., R.G. and A.S. University of Miami: M.A.P.-V., M.L.C. and J.R.G. University of South Carolina: H.H.W., R.K.A. Paris Autism Research: International Sibpair Study: C.B., T.B., C.G. and M.L. Seaver Autism Research Center: J.D.B., K.L.D., E.H. and J.M.S. Stanford University: J.H. and L.L. Vanderbilt University: J.S.S., J.L.H. and S.E.F. University of North Carolina/University of Iowa: J.P., T.H.W., K.J.M. and V.S.

The Autism Genetic Resource Exchange Consortium. D.H.G., M.B., W.T.B., R.M.C., J.N.C., T.C.G., M.H., C.LaJ., D.H.L., C.L.-M., J.M., S.N. C.A.S.-S., S.S., M.S. and R.E.T.

The Collaborative Programs of Excellence in Autism. H.C., G.D., B.D., A.E., P.F., L.K., W.M.McM., N.M., J.M., E.K., P.M.R., G.D.S., M.S., M.A.S., C.S., P.G.T., E.M.W. and C.-E.Y.

The International Molecular Genetic Study of Autism Consortium. France: B.R., C.M., K.W. and M.T. Germany: A.P., B.F., S.M.K., C.S., F.P., S.B., S.F.-M., E.H. and G.S. Greece: J.T., K.P. Italy: E.M., E.B., F.B., S.C. and C.T. The Netherlands: H.V.E., M. de J., C.K., F.K., M.L., C.H. and W.G.S. UK: G.B., P.F.B., M.L.R., E.W., J.G., C.A., J.-A.W., A.P., A.LeC., T.B., H.McC., A.J.B., K.F., G.H., A.H., J.R.P., S.W., A.P.M., G.B., K.K., J.A.L., I.S. and N.S. USA: E.H.C., S.J.G., B.L.L., J.S., C.L., C.C., V.H., D.E.W. and F.V. Canada: E.F.

Scientific management. A.S.

Correspondence to Stephen W Scherer or Bernie Devlin.

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The author declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Binned size distribution of CNVs in batch, plate and filtered analyses. (PDF 93 kb)

Supplementary Fig. 2

Linkage results due to removing families in which affected individuals putatively carry CNV. (PDF 157 kb)

Supplementary Fig. 3

Principal component plot used to infer ancestry. (PDF 188 kb)

Supplementary Fig. 4

Linkage results obtained by analyzing families inferred to be of homogeneous European ancestry. (PDF 696 kb)

Supplementary Table 1

List of 624 CNVs in filtered analysis. (PDF 64 kb)

Supplementary Table 2

List of 254 CNVs in affected individuals. (PDF 380 kb)

Supplementary Table 3

Breakdown of CNVs in affected individuals. (PDF 325 kb)

Supplementary Table 4

List of validated CNVs. (PDF 926 kb)

Supplementary Methods (PDF 61 kb)

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