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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. |
- Watson, Hunna J., et al.
(author)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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In: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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- Braam, Arjan W, et al.
(author)
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Depression and parkinsonism in older Europeans: results from the EURODEP concerted action.
- 2010
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In: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 25:7, s. 679-87
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The prevalence rate of depression among patients with Parkinson's disease (PD) has been estimated at 25%, although prevalence figures range between 7-76%. Relatively few studies on PD and depression are based on random samples in the general population. Some depressive symptoms can also be understood as symptoms of parkinsonism, and the current study aims to describe which 'overlap' symptoms can be identified in a community sample. METHODS: Data are employed from the EURODEP collaboration. Nine study centres, from eight western European countries, provided data on depression (most GMS-AGECAT), depressive symptoms (EURO-D items and anxiety), parkinsonism (self-report of PD or clinical signs of PD), functional disability and dementia diagnosis. RESULTS: Data were complete for 16 313 respondents, aged 65 and older; 306 (1.9%) reported or had signs of parkinsonism. The rate of depression was about twice as high among respondents with parkinsonism (unadjusted Odds Ratio 2.44, 95% Confidence Interval 1.88-3.17), also among those without functional disability. 'Overlap' symptoms between parkinsonism and depression, were represented by motivation and concentration problems, appetite problems and especially the symptom of fatigue (energy loss). However, principal component analysis showed that these 'overlap' symptoms loaded on different factors of the EURO-D scale. CONCLUSIONS: As among clinical patients with PD, depression is highly common in community dwelling older people with parkinsonism, even among those without functional disability. Although fatigue did not strongly relate to motivational symptoms, both types of 'overlap' symptoms possibly trigger a final common pathway towards a full depressive syndrome. Copyright (c) 2009 John Wiley & Sons, Ltd.
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4. |
- Mellqvist Fässberg, Madeleine, et al.
(author)
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Functional disability and death wishes in older Europeans: results from the EURODEP concerted action.
- 2014
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In: Social psychiatry and psychiatric epidemiology. - : Springer Science and Business Media LLC. - 1433-9285 .- 0933-7954. ; 49:9, s. 1475-1482
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Journal article (peer-reviewed)abstract
- Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life.
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