| 1. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)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. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 3. |
- Kahn, Justine M., et al.
(författare)
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Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases
- 2020
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Ingår i: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 4:9, s. 2084-2094
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Tidskriftsartikel (refereegranskat)abstract
- We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). Weincluded 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.
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| 4. |
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| 5. |
- Edem, Idara J., et al.
(författare)
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External injuries, trauma and avoidable deaths in Agincourt, South Africa : a retrospective observational and qualitative study
- 2019
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Injury burden is highest in low-income and middle-income countries. To reduce avoidable deaths, it is necessary to identify health system deficiencies preventing timely, quality care. We developed criteria to use verbal autopsy (VA) data to identify avoidable deaths and associated health system deficiencies.Setting: Agincourt, a rural Bushbuckridge municipality, Mpumalanga Province, South Africa.Participants: Agincourt Health and Socio-Demographic Surveillance System and healthcare providers (HCPs) from local hospitals.Methods: A literature review to explore definitions of avoidable deaths after trauma and barriers to access to care using the ‘three delays framework’ (seeking, reaching and receiving care) was performed. Based on these definitions, this study developed criteria, applicable for use with VA data, for identifying avoidable death and which of the three delays contributed to avoidable deaths. These criteria were then applied retrospectively to the VA-defined category external injury deaths (EIDs—a subset of which are trauma deaths) from 2012 to 2015. The findings were validated by external expert review. Key informant interviews (KIIs) with HCPs were performed to further explore delays to care.Results: Using VA data, avoidable death was defined with a focus on survivability, using level of consciousness at the scene and ability to seek care as indicators. Of 260 EIDs (189 trauma deaths), there were 104 (40%) avoidable EIDs and 78 (30%) avoidable trauma deaths (41% of trauma deaths). Delay in receiving care was the largest contributor to avoidable EIDs (61%) and trauma deaths (59%), followed by delay in seeking care (24% and 23%) and in reaching care (15% and 18%). KIIs revealed context-specific factors contributing to the third delay, including difficult referral systems.Conclusions: A substantial proportion of EIDs and trauma deaths were avoidable, mainly occurring due to facility-based delays in care. Interventions, including strengthening referral networks, may substantially reduce trauma deaths.
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| 6. |
- Gomez-Olive, Francesc Xavier, et al.
(författare)
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Variations in disability and quality of life with age and sex between eight lower income and middle-income countries : data from the INDEPTH WHO-SAGE collaboration
- 2017
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disability and quality of life are key outcomes for older people. Little is known about how these measures vary with age and gender across lower income and middle-income countries; such information is necessary to tailor health and social care policy to promote healthy ageing and minimise disability.Methods: We analysed data from participants aged 50 years and over from health and demographic surveillance system sites of the International Network for the Demographic Evaluation of Populations and their Health Network in Ghana, Kenya, Tanzania, South Africa, Vietnam, India, Indonesia and Bangladesh, using an abbreviated version of the WHO Study on global AGEing survey instrument. We used the eight-item WHO Quality of Life (WHOQoL) tool to measure quality of life and theWHO Disability Assessment Schedule, version 2 (WHODAS-II) tool to measure disability. We collected selected health status measures via the survey instrument and collected demographic and socioeconomic data from linked surveillance site information. We performed regression analyses to quantify differences between countries in the relationship between age, gender and both quality of life and disability, and we used anchoring vignettes to account for differences in interpretation of disability severity.Results: We included 43 935 individuals in the analysis. Mean age was 63.7 years (SD 9.7) and 24 434 (55.6%) were women. In unadjusted analyses across all countries, WHOQoL scores worsened by 0.13 points (95% CI 0.12 to 0.14) per year increase in age and WHODAS scores worsened by 0.60 points (95% CI 0.57 to 0.64). WHODAS-II and WHOQoL scores varied markedly between countries, as did the gradient of scores with increasing age. In regression analyses, differences were not fully explained by age, socioeconomic status, marital status, education or health factors. Differences in disability scores between countries were not explained by differences in anchoring vignette responses.Conclusions: The relationship between age, sex and both disability and quality of life varies between countries. The findings may guide tailoring of interventions to individual country needs, although these associations require further study.
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| 7. |
- Harling, Guy, et al.
(författare)
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Impairment in Activities of Daily Living, Care Receipt, and Unmet Needs in a Middle-Aged and Older Rural South African Population : Findings From the HAALSI Study
- 2020
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Ingår i: Journal of Aging and Health. - : Sage Publications. - 0898-2643 .- 1552-6887. ; 32:5-6, s. 296-307
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The objective of this study is to analyze the degree to which care needs are met in an aging rural African population. Method: Using data from the Health and Aging in Africa: Longitudinal Study of an INDEPTH Community (HAALSI) baseline survey, which interviewed 5,059 adults aged older than 40 years in rural South Africa, we assessed the levels of limitations in activities of daily living (ADLs) and in unmet care for these ADLs, and evaluated their association with sociodemographic and health characteristics. Results: ADL impairment was reported by 12.2% of respondents, with the proportion increasing with age. Among those with ADL impairment, 23.9% reported an unmet need and 51.4% more a partially met need. Relatives provided help most often; formal care provision was rare. Unmet needs were more frequent among younger people and women, and were associated with physical and cognitive deficits, but not income or household size. Discussion: Unmet care needs in rural South Africa are often found among individuals less expected to require care.
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| 8. |
- Payne, Collin F., et al.
(författare)
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Cross-sectional relationship between haemoglobin concentration and measures of physical and cognitive function in an older rural South African population
- 2018
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ Publishing Group Ltd. - 0143-005X .- 1470-2738. ; 72:9, s. 796-802
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Tidskriftsartikel (refereegranskat)abstract
- Background: Age cohort differences in haemoglobin concentrations and associations with physical and cognitive performance among populations of lower income and middle-income countries have not previously been described. We examined the association between these factors among older men and women in rural South Africa.Methods: We analysed cross-sectional data from a population-based study of rural South African men and women aged 40 and over (n=4499), with data drawn from questionnaire responses, a cognitive battery, objective physical function tests and blood tests. Anaemia was defined as a haemoglobin concentration <12 g/dL for women and <13 g/dL for men. We related haemoglobin concentrations to each of age, grip strength, walk speed and a latent cognitive function z-score for men and women separately. We used unadjusted correlations and linear models to adjust for comorbidities and inflammation.Results: In total, 1042 (43.0%) women and 833 (40.1%) men were anaemic. Haemoglobin concentrations were inversely correlated with age for men but not for women; in adjusted analyses, haemoglobin was 0.3 g/dL lower per decade older for men (95% CI 0.2 to 0.4 g/dL). In adjusted analyses, haemoglobin concentration was independently associated with grip strength in women (B=0.391, 95% CI 0.177 to 0.605), but this did not reach significance in men (B=0.266, 95% CI -0.019 to 0.552); no associations were observed between haemoglobin levels and walk speed or cognitive score.Conclusions: Anaemia was prevalent in this study population of middle-aged and older, rural South African adults, but in contrast to high-income countries, it was not associated with poor physical or cognitive function. Our findings need to be replicated in other populations.
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| 9. |
- Payne, Collin F., et al.
(författare)
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Prevalence and correlates of frailty in an older rural African population : findings from the HAALSI cohort study
- 2017
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Frailty is a key predictor of death and dependency, yet little is known about frailty in sub-Saharan Africa despite rapid population ageing. We describe the prevalence and correlates of phenotypic frailty using data from the Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community cohort.Methods: We analysed data from rural South Africans aged 40 and over. We used low grip strength, slow gait speed, low body mass index, and combinations of self-reported exhaustion, decline in health, low physical activity and high self-reported sedentariness to derive nine variants of a phenotypic frailty score. Each frailty category was compared with self-reported health, subjective wellbeing, impairment in activities of daily living and the presence of multimorbidity. Cox regression analyses were used to compare subsequent all-cause mortality for non-frail (score 0), pre-frail (score 1–2) and frail participants (score 3+).Results: Five thousand fifty nine individuals (mean age 61.7 years, 2714 female) were included in the analyses. The nine frailty score variants yielded a range of frailty prevalences (5.4% to 13.2%). For all variants, rates were higher in women than in men, and rose steeply with age. Frailty was associated with worse subjective wellbeing, and worse self-reported health. Both prefrailty and frailty were associated with a higher risk of death during a mean 17 month follow up for all score variants (hazard ratios 1.29 to 2.41 for pre-frail vs non-frail; hazard ratios 2.65 to 8.91 for frail vs non-frail).Conclusions: Phenotypic frailty could be measured in this older South African population, and was associated with worse health, wellbeing and earlier death.
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| 10. |
- Wade, Alisha N, et al.
(författare)
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Multimorbidity and mortality in an older, rural black South African population cohort with high prevalence of HIV findings from the HAALSI Study
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Multimorbidity is associated with mortality in high-income countries. Our objective was to investigate the relationship between multimorbidity (≥2 of the following chronic medical conditions: hypertension, diabetes, dyslipidaemia, anaemia, HIV, angina, depression, post-traumatic stress disorder, alcohol dependence) and all-cause mortality in an older, rural black South African population. We further investigated the relationship between HIV multimorbidity (HIV as part of the multimorbidity cluster) and mortality, while testing for the effect of frailty in all models.Design: Population cohort study.Setting: Agincourt subdistrict of Mpumalanga province, South Africa.Participants: 4455 individuals (54.7% female), aged ≥40 years (median age 61 years, IQR 52-71) and resident in the study area.Primary and secondary outcome measures: The primary outcome measure was time to death and the secondary outcome measure was likelihood of death within 2 years of the initial study visit. Mortality was determined during annual population surveillance updates.Results: 3157 individuals (70.9%) had multimorbidity; 29% of these had HIV. In models adjusted for age and sociodemographic factors, multimorbidity was associated with greater risk of death (women: HR 1.72; 95% CI: 1.18 to 2.50; men: HR 1.46; 95% CI: 1.09 to 1.95) and greater odds of dying within 2 years (women: OR 2.34; 95% CI: 1.32 to 4.16; men: OR 1.51; 95% CI: 1.02 to 2.24). HIV multimorbidity was associated with increased risk of death compared with non-HIV multimorbidity in men (HR 1.93; 95% CI: 1.05 to 3.54), but was not statistically significant in women (HR 1.85; 95% CI: 0.85 to 4.04); when detectable, HIV viral loads were higher in men (p=0.021). Further adjustment for frailty slightly attenuated the associations between multimorbidity and mortality risk (women: HR 1.55; 95% CI: 1.06 to 2.26; men: HR 1.36; 95% CI: 1.01 to 1.82), but slightly increased associations between HIV multimorbidity and mortality risk.Conclusions: Multimorbidity is associated with mortality in this older black South African population. Health systems which currently focus on HIV should be reorganised to optimise identification and management of other prevalent chronic diseases.
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