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  • Original Research Article
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Analysis of the RELN gene as a genetic risk factor for autism

Molecular Psychiatry volume 10, pages 563–571 (2005)Cite this article

Abstract

Several genome-wide screens have indicated the presence of an autism susceptibility locus within the distal long arm of chromosome 7 (7q). Mapping at 7q22 within this region is the candidate gene reelin (RELN). RELN encodes a signaling protein that plays a pivotal role in the migration of several neuronal cell types and in the development of neural connections. Given these neurodevelopmental functions, recent reports that RELN influences genetic risk for autism are of significant interest. The total data set consists of 218 Caucasian families collected by our group, 85 Caucasian families collected by AGRE, and 68 Caucasian families collected at Tufts University were tested for genetic association of RELN variants to autism. Markers included five single-nucleotide polymorphisms (SNPs) and a repeat in the 5′-untranslated region (5′-UTR). Tests for association in Duke and AGRE families were also performed on four additional SNPs in the genes PSMC2 and ORC5L, which flank RELN. Family-based association analyses (PDT, Geno-PDT, and FBAT) were used to test for association of single-locus markers and multilocus haplotypes with autism. The most significant association identified from this combined data set was for the 5′-UTR repeat (PDT P-value=0.002). These analyses show the potential of RELN as an important contributor to genetic risk in autism.

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Acknowledgements

We wish to thank the patients with autism and family members who agreed to participate in this study. We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Cure Autism Now. We also thank the personnel of the Center for Human Genetics at Duke University Medical Center, who provided a great deal of support and input on this project. This research was supported in part by National Institutes of Health (NIH) program project grant NS26630, NIH R01 grants HD36701 and NS36768, and by the National Alliance of Autism Research (NAAR) through a gift from Audrey Flack and H Robert Marcus. The research conducted in this study complies with current US laws.

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Authors and Affiliations

  1. Department of Medicine, Center for Human Genetics, IGSP, Duke University Medical Center, Durham, NC, USA

    D A Skaar, Y Shao, J E Stenger, J Jaworski, E R Martin, G R DeLong, A E Ashley-Koch, M L Cuccaro, J R Gilbert & M A Pericak-Vance

  2. Center for Human Genetics Research and Department of Molecular Physiology and Biophysics Vanderbilt University Medical Center, Nashville, TN, USA

    J L Haines, J H Moore, J L McCauley & J S Sutcliffe

  3. Department of Psychiatry, Tufts University/New England Medical Center, Boston, MA, USA

    S E Folstein

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  1. D A Skaar
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Correspondence to M A Pericak-Vance.

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Skaar, D., Shao, Y., Haines, J. et al. Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry 10, 563–571 (2005). https://doi.org/10.1038/sj.mp.4001614

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