Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Within the Million Veteran Program (Mvp) Cohort

Kimbrel, Nate; Ashley–Koch, Allison; Beckham, Jean C.; Hauser, Beth; Hauser, M.

doi:10.1016/j.euroneuro.2022.07.062

Cited by 4 publications

(5 citation statements)

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“…3f,g). The rs77641763 was associated with suicidal thoughts and behaviors 24 . The other top significant genes include CNNM2, GBF1, NOLC1, NT5C2 and TRIM (Fig.…”

Section: Genome-wide-significant Associations With Environmental Psyc...mentioning

confidence: 99%

“…Finding multiple modes between urban living environmental profiles and psychiatric symptom groups. After determining the significance of the first canonical correlate, we removed the effect of the first set of canonical vectors using projection deflation 17,18,24 . This is important to keep in mind to correctly interpret our findings, in particular the GWAS analysis.…”

Section: Multivariate Relation Of Urban Living Environmental Profiles...mentioning

confidence: 99%

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Effects of urban living environments on mental health in adults

Xu,

Liu,

Polemiti

et al. 2023

Nat Med

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Urban-living individuals are exposed to many environmental factors that may combine and interact to influence mental health. While individual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city relates to brain and mental health, and how this is moderated by genetic factors. Using the data of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation analyses to investigate the relationships between urban environments and psychiatric symptoms. We found an environmental profile of social deprivation, air pollution, street network and urban land-use density that was positively correlated with an affective symptom group (r = 0.22, Pperm < 0.001), mediated by brain volume differences consistent with reward processing, and moderated by genes enriched for stress response, including CRHR1, explaining 2.01% of the variance in brain volume differences. Protective factors such as greenness and generous destination accessibility were negatively correlated with an anxiety symptom group (r = 0.10, Pperm < 0.001), mediated by brain regions necessary for emotion regulation and moderated by EXD3, explaining 1.65% of the variance. The third urban environmental profile was correlated with an emotional instability symptom group (r = 0.03, Pperm < 0.001). Our findings suggest that different environmental profiles of urban living may influence specific psychiatric symptom groups through distinct neurobiological pathways.

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“…3f,g). The rs77641763 was associated with suicidal thoughts and behaviors 24 . The other top significant genes include CNNM2, GBF1, NOLC1, NT5C2 and TRIM (Fig.…”

Section: Genome-wide-significant Associations With Environmental Psyc...mentioning

confidence: 99%

Section: Multivariate Relation Of Urban Living Environmental Profiles...mentioning

confidence: 99%

Effects of urban living environments on mental health in adults

Xu,

Liu,

Polemiti

et al. 2023

Nat Med

View full text Add to dashboard Cite

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“…Dot color indicates enrichment significance as –log10(P) with darker reds indicating greater significance. We interpret the suicide results cautiously as this GWAS did not clearly control for MDD 40 which may confound the enrichment pattern. mdd2019* summary statistics did not include data from 23andMe.…”

Section: Resultsmentioning

confidence: 99%

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity

Yao,

Harder,

Darki

et al. 2024

Preprint

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Understanding the temporal and spatial brain locations etiological for psychiatric disorders is essential for targeted neurobiological research. Integration of genomic insights from genome-wide association studies with single-cell transcriptomics is a powerful approach although past efforts have necessarily relied on mouse atlases. Leveraging a comprehensive atlas of the adult human brain, we prioritized cell types via the enrichment of SNP-heritabilities for brain diseases, disorders, and traits, progressing from individual cell types to brain regions. Our findings highlight specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals important patterns for schizophrenia with distinct subregions in the hippocampus and amygdala exhibiting the highest significance. Cerebral cortical regions display similar enrichments despite the known prefrontal dysfunction in those with schizophrenia highlighting the importance of subcortical connectivity. Using functional MRI connectivity from cases with schizophrenia and neurotypical controls, we identified brain networks that distinguished cases from controls that also confirmed involvement of the central and lateral amygdala, hippocampal body, and prefrontal cortex. Our findings underscore the value of single-cell transcriptomics in decoding the polygenicity of psychiatric disorders and offer a promising convergence of genomic, transcriptomic, and brain imaging modalities toward common biological targets.

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“…total N = 549,743; 29,782 cases) identified two loci reaching genomewide significance for SA on chromosomes 6 (p = 1.97 Â 10 À8 ) and 7 (p = 1.91 Â 10 À10 ) (Mullins et al, 2022). The locus on chromosome 7 remained significant after conditioning on psychiatric disorders, and was independently replicated within the Million Veteran Program adhesion, regulation of cell proliferation, transmission of nerve impulse (SD; Galfalvy et al, 2013), oxytocin signaling, glutamatergic synapse, axon guidance, calcium signaling, circadian entrainment, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm (SA; Kimbrel et al, 2022). A recent analysis on SD by Sokolowski and Wasserman (2021) pooled information from published GWAS and whole exome studies to group identified genes together, finding evidence for contributions from chromosome 19 as well as a set of 54 "core" genes involved in synaptic and nervous system development.…”

Section: Genome-wide Association Studies and Genome-wide Cnvmentioning

confidence: 99%

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

Mirza

Docherty

Bakian

et al. 2022

American J of Med Genetics Pt B

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Suicide is a multifaceted and poorly understood clinical outcome, and there is an urgent need to advance research on its phenomenology and etiology. Epidemiological studies have demonstrated that suicidal behavior is heritable, suggesting that genetic and epigenetic information may serve as biomarkers for suicide risk. Here we systematically review the literature on genetic and epigenetic alterations observed in phenotypes across the full range of self-injurious thoughts and behaviors (SITB). We included 577 studies focused on genome-wide and epigenome-wide associations, candidate genes (SNP and methylation), noncoding RNAs, and histones. Convergence of specific genes is limited across units of analysis, although pathway-based analyses do indicate nervous system development and function and immunity/inflammation as potential underlying mechanisms of SITB. We provide suggestions for future work on the genetic and epigenetic correlates of SITB with a specific focus on measurement issues.

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Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Within the Million Veteran Program (Mvp) Cohort

Cited by 4 publications

References 0 publications

Effects of urban living environments on mental health in adults

Effects of urban living environments on mental health in adults

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

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