title: Whole-gene sequencing investigation of SAT1 in attempted suicide.
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 10 kb 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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Monson
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Kelly
authors.initials: K
authors.lastname: de Klerk
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Sophia C
authors.initials: SC
authors.lastname: Gaynor
authors.affiliation: Interdisciplinary PhD Program in Genetics, University of Iowa Carver College of Medicine, Iowa City, Iowa.|McDonnel Genome Institute, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Alex H
authors.initials: AH
authors.lastname: Wagner
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Breen
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Meredith
authors.initials: M
authors.lastname: Parsons
authors.affiliation: Departments of Biomedical Engineering and Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Casavant
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zandi
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Willour
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D059020:Suicidal Ideation; D013405:Suicide / Q000523:psychology; D013406:Suicide, Attempted / Q000523:psychology*; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D000099228:Diamine N-Acetyltransferase
keywords: bipolar disorder; next-generation sequencing; spermine/spermidine N1-acetyltransferase 1; suicidal behavior