A pilot genome wide association and gene expression array study of suicide with and without major depression
Open accessAbstract
OBJECTIVES: Suicide is partly heritable but the responsible genes have not been identified. We conducted a gene-centric, low coverage single nucleotide polymorphism (SNP) pilot genome-wide association study (GWAS) seeking new candidate regions in suicides with and without depression, combined with gene expression assay of brain tissue. METHODS: Ninety-nine Caucasian subjects, including 68 who completed suicide and 31 who died suddenly from other causes, were genotyped postmortem using GeneChip® Mapping 50K Xba. Clinical data were obtained from relatives. SNPs with Hardy-Weinberg equilibrium P values below 0.001 were excluded from analysis. Illumina chip expression arrays assayed the transcriptome in prefrontal cortex in a drug-free subgroup. RESULTS: GWAS analysis (cutoff P < 0.001) yielded 58 SNPs, 22 of them in or near 19 known genes, with risk allele-associated odds ratios between 2.7 and 6.9. Diagnosis of mood disorder did not explain the associations. Some of the SNPs matched into four functional groups in gene ontology. Gene expression in the prefrontal and the anterior cingulate cortex for these 19 genes was measured on a separate, though overlapping, sample of suicides and seven of 19 genes showed altered expression in suicides as compared with controls, especially in immune system related genes. CONCLUSIONS: Matching GWAS findings with expression data assesses functional effect of new candidate genes in suicide, and is an alternative form of confirmation or replication study. Results highlight a role for neuroimmunological effects in suicidal behaviour.
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These studies identified a total of 32 single nucleotide polymorphisms (SNPs) of interest, of which multiple SNPs were associated with the TBX20 locus.
“These studies identified a total of 32 single nucleotide polymorphisms (SNPs) of interest, of which multiple SNPs were associated with the TBX20 locus 41,42 .”
From Suicide and suicide risk (2019) · cites this paper as [42]
The Results (SNP analyses; page unavailable) report 58 SNPs meeting the study’s significance cutoff, including 22 in or near 19 known genes, so the paper supports identifying SNPs of interest. It does not report a total of 32 across the two cited studies, and the passages retrieved for TBX20 do not identify that locus or associate multiple SNPs with it. (LLM, conf=0.83)
Experimental — accuracy not yet measuredOnly a handful of GWAS have included suicide as a primary phenotype.
“Of note, only a handful of GWAS have included suicide as a primary phenotype 40-42 .”
From Suicide and suicide risk (2019) · cites this paper as [42]
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- Authors
- Galfalvy, H., Zalsman, G., Huang, Y.-Y., Murphy, L., Rosoklija, G., Dwork, A. J., Haghighi, F., Arango, V., & Mann, J. J.
- Affiliations
- New York State Psychiatric Institute (US)
- Tel Aviv University (IL)
- Macedonian Academy of Sciences and Arts (MK)
- Corresponding author
- Mann, J. John
- Venue
- The World Journal of Biological Psychiatry
- Publisher
- Informa UK Limited
- Published
- 2011-11-07
- Volume
- 14
- Issue
- 8
- Pages
- 574-582
- ISSN
- 1562-2975 (ISSN-L)
- 1814-1412
- PMC
- PMC3493880
- OpenAlex
- W2044265147
- Cited by
- 77
- References
- 39
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 13 · 2015: 3 · 2014: 11 · 2013: 1 · 2012: 3
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The World Journal of Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH 62185, MH082041, R01MH064168, MH64168, R01MH082041, MH-40210, R01MH040210, K25MH074068, P50MH062185)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- suicide, major depressive disorder, genome-wide association study, single nucleotide polymorphisms, candidate genes, gene expression, prefrontal cortex, anterior cingulate cortex, neuroimmunology, immune-related genes
- MeSH terms
- Adult, Aged, Brain, Major Depressive Disorder, Female, Gene Expression Regulation, Genotype, Gyrus Cinguli, Humans, Male, Middle Aged, Pilot Projects, Suicide, Neuroimmunomodulation, Prefrontal Cortex, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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