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A high-density SNP genome-wide linkage scan in a large autism extended pedigree

Molecular Psychiatry volume 14, pages 590–600 (2009)Cite this article

Abstract

We performed a high-density, single nucleotide polymorphism (SNP), genome-wide scan on a six-generation pedigree from Utah with seven affected males, diagnosed with autism spectrum disorder. Using a two-stage linkage design, we first performed a nonparametric analysis on the entire genome using a 10K SNP chip to identify potential regions of interest. To confirm potentially interesting regions, we eliminated SNPs in high linkage disequilibrium (LD) using a principal components analysis (PCA) method and repeated the linkage results. Three regions met genome-wide significance criteria after controlling for LD: 3q13.2–q13.31 (nonparametric linkage (NPL), 5.58), 3q26.31–q27.3 (NPL, 4.85) and 20q11.21–q13.12 (NPL, 5.56). Two regions met suggestive criteria for significance 7p14.1–p11.22 (NPL, 3.18) and 9p24.3 (NPL, 3.44). All five chromosomal regions are consistent with other published findings. Haplotype sharing results showed that five of the affected subjects shared more than a single chromosomal region of interest with other affected subjects. Although no common autism susceptibility genes were found for all seven autism cases, these results suggest that multiple genetic loci within these regions may contribute to the autism phenotype in this family, and further follow-up of these chromosomal regions is warranted.

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Acknowledgements

This work was supported by R01 MH069359, 5 U19 HD035476 (one of the NICHD Collaborative Programs of Excellence in Autism), the Utah Autism Foundation and by GCRC grant number M01-RR00064 from the National Center for Research Resources. Partial support for all datasets within the Utah Population Database (UPDB) was provided by the University of Utah Huntsman Cancer Institute. We thank Dr Sally Ozonoff for assistance with diagnoses of subjects, and our staff whose countless hours of work have made this study possible. We also greatly appreciate the time and effort given by the family members who participated in this study.

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Authors and Affiliations

  1. Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

    K Allen-Brady, J Miller, J Stevens, H Block, M Farley, L Krasny, C Pingree, J Lainhart, M Leppert, W M McMahon & H Coon

  2. Department of Human Genetics, University of Utah, Salt Lake City, UT, USA

    N Matsunami

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  1. K Allen-Brady
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Correspondence to K Allen-Brady.

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Electronic-Database Information

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

Utah Population Database (UPDB), http://www.hci.utah.edu/groups/ppr/

HapMap, http://www.hapmap.org/

SNPHAP, http://www-gene.cimr.cam.ac.uk/clayton/software/

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Allen-Brady, K., Miller, J., Matsunami, N. et al. A high-density SNP genome-wide linkage scan in a large autism extended pedigree. Mol Psychiatry 14, 590–600 (2009). https://doi.org/10.1038/mp.2008.14

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