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Examination of association of genes in the serotonin system to autism

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Abstract

Autism is characterized as one of the pervasive developmental disorders, a spectrum of often severe behavioral and cognitive disturbances of early development. The high heritability of autism has driven multiple efforts to identify genetic variation that increases autism susceptibility. Numerous studies have suggested that variation in peripheral and central metabolism of serotonin (5-hydroxytryptamine) may play a role in the pathophysiology of autism. We screened 403 autism families for 45 single nucleotide polymorphisms in ten serotonin pathway candidate genes. Although genome-wide linkage scans in autism have provided support for linkage to various loci located within the serotonin pathway, our study does not provide strong evidence for linkage to any specific gene within the pathway. The most significant association (p = 0.0002; p = 0.02 after correcting for multiple comparisons) was found at rs1150220 (HTR3A) located on chromosome 11 (∼113 Mb). To test specifically for multilocus effects, multifactor dimensionality reduction was employed, and a significant two-way interaction (p value = 0.01) was found between rs10830962, near MTNR1B (chromosome11; 92,338,075 bp), and rs1007631, near SLC7A5 (chromosome16; 86,413,596 bp). These data suggest that variation within genes on the serotonin pathway, particularly HTR3A, may have modest effects on autism risk.

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Acknowledgments

We wish to thank both the patients with autism and their family members who agreed to participate in this study, as well as the personnel of the Center for Human Genetics Research at Vanderbilt University and the Miami Institute for Human Genomics at the University of Miami. We would like to thank M.J. Allen for her excellent technical support. This research was supported in part by National Institutes of Health (NIH) program project grant NS026630 (MPV, JLH) and NIH R01 grant MH080647.

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Authors and Affiliations

  1. Center for Human Genetics Research, Vanderbilt University Medical Center, 519 Light Hall, Nashville, TN, 37232-0700, USA

    B. M. Anderson, N. C. Schnetz-Boutaud, J. Bartlett, A. M. Wotawa & J. L. Haines

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

    B. M. Anderson, N. C. Schnetz-Boutaud, J. Bartlett, A. M. Wotawa & J. L. Haines

  3. Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA

    M. L. Cuccaro, J. R. Gilbert & M. A. Pericak-Vance

  4. W.S. Hall Psychiatric Institute, University of South Carolina, Columbia, SC, USA

    H. H. Wright & R. K. Abramson

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Anderson, B.M., Schnetz-Boutaud, N.C., Bartlett, J. et al. Examination of association of genes in the serotonin system to autism. Neurogenetics 10, 209–216 (2009). https://doi.org/10.1007/s10048-009-0171-7

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