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- Mullins, Niamh, et al.
(author)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Journal article (peer-reviewed)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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2. |
- Haahr, Thor, et al.
(author)
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Vaginal dysbiosis in pregnancy associates with risk of emergency caesarean section: a prospective cohort study
- 2022
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In: Clinical Microbiology and Infection. - Oxford, United Kingdom : Elsevier. - 1198-743X .- 1469-0691. ; 28:4, s. 588-595
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Journal article (peer-reviewed)abstract
- Objectives: To investigate changes in vaginal microbiota during pregnancy, and the association between vaginal dysbiosis and reproductive outcomes.Methods: A total of 730 (week 24) and 666 (week 36) vaginal samples from 738 unselected pregnant women were studied by microscopy (Nugent score) and characterized by 16S rRNA gene sequencing. A novel continuous vaginal dysbiosis score was developed based on these methods using a supervised partial least squares model.Results: Among women with bacterial vaginosis in week 24 (n = 53), 47% (n = 25) also had bacterial vaginosis in week 36. In contrast, among women without bacterial vaginosis in week 24, only 3% (n = 18) developed bacterial vaginosis in week 36. Vaginal samples dominated by Lactobacillus crispatus (OR 0.35, 95% CI 0.20–0.60) and Lactobacillus iners (OR 0.40, 95% CI 0.23–0.68) in week 24 were significantly more stable by week 36 when compared with other vaginal community state types. Vaginal dysbiosis score at week 24 was associated with a significant increased risk of emergency, but not elective, caesarean section (OR 1.37, 955 CI 1.15–1.64, p < 0.001), suggesting a 37% increased risk per standard deviation increase in vaginal dysbiosis score.Conclusions: Changes in vaginal microbiota from week 24 to week 36 of pregnancy correlated with bacterial vaginosis status and vaginal community state type. A novel vaginal dysbiosis score was associated with a significantly increased risk of emergency, but not elective, caesarean section. This was not found for bacterial vaginosis or any vaginal community state type and could point to the importance of investigating vaginal dysbiosis as a nuanced continuum instead of crude clusters.
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