Whole-gene sequencing investigation of SAT1 in attempted suicide

Eric T. Monson, Kelly de Klerk, Sophia C. Gaynor, Alex H. Wagner, Marie E. Breen, Meredith Parsons, Thomas L. Casavant, Peter P Zandi, James Bennett Potash, Virginia L. Willour

Research output: Contribution to journalArticle

Abstract

Suicidal behavior imposes a tremendous cost, with current US estimates reporting approximately 1.3 million suicide attempts and more than 40,000 suicide deaths each year. Several recent research efforts have identified an association between suicidal behavior and the expression level of the spermidine/spermine N1-acetyltransferase 1 (SAT1) gene. To date, several SAT1 genetic variants have been inconsistently associated with altered gene expression and/or directly with suicidal behavior. To clarify the role SAT1 genetic variation plays in suicidal behavior risk, we present a whole-gene sequencing effort of SAT1 in 476 bipolar disorder subjects with a history of suicide attempt and 473 subjects with bipolar disorder but no suicide attempts. Agilent SureSelect target enrichment was used to sequence all exons, introns, promoter regions, and putative regulatory regions identified from the ENCODE project within 10kb of SAT1. Individual variant, haplotype, and collapsing variant tests were performed. Our results identified no variant or assessed region of SAT1 that showed a significant association with attempted suicide, nor did any assessment show evidence for replication of previously reported associations. Overall, no evidence for SAT1 sequence variation contributing to the risk for attempted suicide could be identified. It is possible that past associations of SAT1 expression with suicidal behavior arise from variation not captured in this study, or that causal variants in the region are too rare to be detected within our sample. Larger sample sizes and broader sequencing efforts will likely be required to identify the source of SAT1 expression level associations with suicidal behavior.

Keywords

  • Bipolar disorder
  • Next-generation sequencing
  • Spermine/spermidine N1-acetyltransferase 1
  • Suicidal behavior

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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  • Cite this

    Monson, E. T., de Klerk, K., Gaynor, S. C., Wagner, A. H., Breen, M. E., Parsons, M., Casavant, T. L., Zandi, P. P., Potash, J. B., & Willour, V. L. (Accepted/In press). Whole-gene sequencing investigation of SAT1 in attempted suicide. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. https://doi.org/10.1002/ajmg.b.32462