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Genome-wide association study of suicide attempts in mood disorder patients.

ABSTRACT: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts.The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort.Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety.The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

SUBMITTER: Perlis RH

PROVIDER: S-EPMC3795390 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Genome-wide association study of suicide attempts in mood disorder patients.

Perlis Roy H RH Huang Jie J Purcell Shaun S Fava Maurizio M Rush A John AJ Sullivan Patrick F PF Hamilton Steven P SP McMahon Francis J FJ Schulze Thomas G TG Potash James B JB Zandi Peter P PP Willour Virginia L VL Penninx Brenda W BW Boomsma Dorret I DI Vogelzangs Nicole N Middeldorp Christel M CM Rietschel Marcella M Nöthen Markus M Cichon Sven S Gurling Hugh H Bass Nick N McQuillin Andrew A Hamshere Marian M Craddock Nick N Sklar Pamela P Smoller Jordan W JW

The American journal of psychiatry 20101101 12

<h4>Objective</h4>Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts.<h4>Method</h4>The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment ...[more]

PMID: 21041247

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Project description:Suicidal behavior (SB) has a complex etiology of genes, environment or both. One of the genetic components in SB could be copy number variations (CNVs), since CNVs are implicated in a range of neurodevelopmental disorders. However, a recently published genome-wide and case-control study failed to observe a significant role of CNVs in SB (see E-MTAB-3519). Here we complement those initial observations by conducting a brief CNV-association study, for the first time in a family-based trio-sample with severe suicide attempt (SA) outcome in offspring (n=660 trios; the \GISS\ sample, see http://www.ncbi.nlm.nih.gov/pubmed/23422793 and refs therein). For association testing, we here used the FBAT-CNV methodology (http://www.ncbi.nlm.nih.gov/pubmed/18228561), which allows for CNV association testing directly on the raw intensity values (Illumina \log R ratio\), evaluating any type of CNVs (e.g. de novo or inherited) without reliance on CNV calling algorithms and robust to control selection biases. Here we have deposited these raw logR-values for 88,450 on-chip CNV-loci of the HumanOmni1-Quad_v1 chip, arranged in a standard pedigree format used as input for FBAT-CNV analysis in SVS software (goldenhelix.com): column 1 is the family ID, column 2 is the Subject type (1 = offspring, 2 = mother, 3 = father), column 3 is the father ID (? for missing), column 4 is the mother ID (? for missing), column 5 is the sex (1 = female, 0 = male), column 6 is the affection status (1 = suicide attempt, 0 = not affected) and columns 7 and onward are the logR-values for each CNV-loci as is listed in the header row. We observed experiment-wide significant association (P ≤ 5.6 x 10-7) of two proximal CNVs at chromosome 14 (Illumina markers cnvi0108946 and cnvi0118308, with NCBI 36.3 start positions 22794779 and 22582820). However, these CNV-associations mapped to T-cell receptor regions, and therefore most likely reflect inter-individual variation in somatic rearrangements occurring in white blood cells (as our source of DNA was blood), rather than association with SA. In conclusion, our results did not suggest any major role of CNVs in SA etiology, in line with the results of the recent case-control study (see E-MTAB-3519).

Dataset Information

Genome-wide association study of suicide attempts in mood disorder patients.

Publications

Genome-wide association study of suicide attempts in mood disorder patients.

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