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Evidence for multiple loci from a genome scan of autism kindreds

Molecular Psychiatry volume 11, pages 1049–1060 (2006)Cite this article

Abstract

We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P=0.0009, 83.82 cM), and for the FC group on chromosome 4 (P=0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P=0.003, 0 cM) and 14 (P=0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P=0.0002, 140.06 cM) and 4 (P=0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P=0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.

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Acknowledgements

This research was supported by a program project grant from the National Institute of Child Health and Human Development and the National Institute on Deafness and Communication Disability (PO1HD34565), which is part of the NICHD/NIDCD Collaborative Program of Excellence in Autism. We gratefully acknowledge the contributions of the Diagnostic and Statistical Cores of the UW Autism Program Project, Cathy Brock who assisted in recruitment of participants, Hiep Nguyen for computer support, and the parents and their children who participated in this study. This work was also supported in part by the Veterans Affairs Administration (GDS). Work at the University of Utah was supported by NICHD Grant HD35476, Grant MO1-RR00064 from the National Center for Research Resources, the Devonshire Foundation and the Utah Autism Research Foundation.

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Authors and Affiliations

  1. Geriatrics Research Education and Clinical Center, Puget Sound Veterans Affairs Medical Center, Seattle, WA, USA

    G D Schellenberg, L Leong & C-E Yu

  2. Department of Medicine, Gerontology and Geriatric Medicine, University of Washington, Seattle, WA, USA

    G D Schellenberg, L Leong & C-E Yu

  3. Department of Neurology, University of Washington, Seattle, WA, USA

    G D Schellenberg

  4. Department of Pharmacology, University of Washington, Seattle, WA, USA

    G D Schellenberg

  5. Department of Psychology and the Center on Human Development and Disability, University of Washington, Seattle, WA, USA

    G Dawson & J Munson

  6. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA

    G Dawson & A Estes

  7. Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA

    Y J Sung & E M Wijsman

  8. Department of Biostatistics, University of Washington, Seattle, WA, USA

    E Rosenthal, J Rothstein & E M Wijsman

  9. Department of Pediatrics, University of California, Irvine, CA, USA

    P Flodman & M A Spence

  10. Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of Utah, Salt Lake City, UT, USA

    M Smith, H Coon & W M McMahon

  11. Department of OB/GYN, University of Rochester Medical Center, Rochester, NY, USA

    C Stodgell & P M Rodier

  12. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    N Minshew

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  1. G D Schellenberg
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Correspondence to G D Schellenberg.

Additional information

Electronic-Database Information

The URLs for data presented herein are as follows:

 Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim.

 Rutgers Genetic Map (MAP-O-MAT), http://compgen.rutgers.edu/mapomat.

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Schellenberg, G., Dawson, G., Sung, Y. et al. Evidence for multiple loci from a genome scan of autism kindreds. Mol Psychiatry 11, 1049–1060 (2006). https://doi.org/10.1038/sj.mp.4001874

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