Suicidal ideation, suicide attempt (SA) and suicide are significantly heritable phenotypes. However, the extent to which these phenotypes share genetic architecture is unclear. This question is of ...great relevance to determining key risk factors for suicide, and to alleviate the societal burden of suicidal thoughts and behaviors (STBs). To help address the question of heterogeneity, consortia efforts have recently shifted from a focus on suicide within the context of major psychopathology (e.g. major depressive disorder, schizophrenia) to suicide as an independent entity. Recent molecular studies of suicide risk by members of the Psychiatric Genomics Consortium and the International Suicide Genetics Consortium have identified genome-wide significant loci associated with SA and with suicide death, and have examined these phenotypes within and outside of the context of major psychopathology. This review summarizes important insights from epidemiological and biometrical research on suicide, and discusses key empirical findings from molecular genetic examinations of STBs. Polygenic risk scores for these phenotypes have been observed to be associated with case−control status and other risk phenotypes. In addition, estimated shared genetic covariance with other phenotypes suggests specific medical and psychiatric risks beyond major depressive disorder. Broadly, molecular studies suggest a complexity of suicide etiology that cannot simply be accounted for by depression. Discussion of the state of suicide genetics, a growing field, also includes important ethical and clinical implications of studying the genetic risk of suicide.
This article provides a review of the ethical considerations that drive research policy and practice related to the genetic study of suicide. As the tenth cause of death worldwide, suicide ...constitutes a substantial public health concern. Biometrical studies and population‐based molecular genetic studies provide compelling evidence of the utility of investigating genetic underpinnings of suicide. International, federal, and institutional policies regulating research are explored through the lenses of the ethical principles of autonomy, beneficence, non‐maleficence, and justice. Trapped between the Common Rule's definition of human subjects, and the Health Insurance Portability and Accountability Act's protected information, suicide decedent data occupy an ethical gray area fraught with jurisdictional, legal, and social implications. Two avenues of research, biobanks and psychological autopsies, provide tangible application for the ethical principles examining the risks to participants and their families. Additionally, studies surveying public opinion about research methods, especially broad consent, are explored. Our approach of applying the four ethical principles to policy, sample collection, data storage, and secondary research applications can also be applied to genetic research with other populations. We conclude that broad consent for secondary research, as well as next‐of‐kin at the time of autopsy, serve to satisfy privacy and confidentiality under the ethical principle of autonomy. We recommend ongoing ethical evaluation of research policy and practice.
Precision medicine in psychiatry is on the rise, and depression and obesity - two highly prevalent, comorbid and well-characterised phenotypes - are optimal targets for the approach. Add the bedrock ...susceptibility gene,
, and Riviera
have identified a constellation of factors that could enhance clinical treatment of both disorders.
Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). ...Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals.
Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection = 56.06; 93.4% male; 82.7% European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category; 306 (31.1%) reported at least one post-acute COVID-19 symptom at 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates.
The asthma PRS was associated with severe COVID-19 category (odds ratio OR = 1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (β = .09, p = .01), independently of respiratory disease diagnosis. Severe COVID-19 category was also associated with the allergic disease PRS (OR = 1.97, 1.26-3.07) and the PRS for COVID-19 hospitalization (OR = 1.35, 1.01-1.82). PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity.
Recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population.
Death by suicide is a highly preventable yet growing worldwide health crisis. To date, there has been a lack of adequately powered genomic studies of suicide, with no sizable suicide death cohorts ...available for analysis. To address this limitation, the authors conducted the first comprehensive genomic analysis of suicide death using previously unpublished genotype data from a large population-ascertained cohort.
The analysis sample comprised 3,413 population-ascertained case subjects of European ancestry and 14,810 ancestrally matched control subjects. Analytical methods included principal component analysis for ancestral matching and adjusting for population stratification, linear mixed model genome-wide association testing (conditional on genetic-relatedness matrix), gene and gene set-enrichment testing, and polygenic score analyses, as well as single-nucleotide polymorphism (SNP) heritability and genetic correlation estimation using linkage disequilibrium score regression.
Genome-wide association analysis identified two genome-wide significant loci (involving six SNPs: rs34399104, rs35518298, rs34053895, rs66828456, rs35502061, and rs35256367). Gene-based analyses implicated 22 genes on chromosomes 13, 15, 16, 17, and 19 (q<0.05). Suicide death heritability was estimated at an h
value of 0.25 (SE=0.04) and a value of 0.16 (SE=0.02) when converted to a liability scale. Notably, suicide polygenic scores were significantly predictive across training and test sets. Polygenic scores for several other psychiatric disorders and psychological traits were also predictive, particularly scores for behavioral disinhibition and major depressive disorder.
Multiple genome-wide significant loci and genes were identified and polygenic score prediction of suicide death case-control status was demonstrated, adjusting for ancestry, in independent training and test sets. Additionally, the suicide death sample was found to have increased genetic risk for behavioral disinhibition, major depressive disorder, depressive symptoms, autism spectrum disorder, psychosis, and alcohol use disorder compared with the control sample.
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