| 1. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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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. |
- Kogevinas, Manolis, et al.
(författare)
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Exposure to substances in the workplace and new-onset asthma : an international prospective population-based study (ECRHS-II)
- 2007
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 370:9584, s. 336-341
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Tidskriftsartikel (refereegranskat)abstract
- Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre. Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.
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| 4. |
- Le Moual, Nicole, et al.
(författare)
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Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:2, s. 374-386
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Tidskriftsartikel (refereegranskat)abstract
- Occupational exposure is a well-recognised modifiable risk factor for asthma, but the relationship between occupational exposure and asthma control has not been studied. We aimed to study this association among working-age adults from the European Community Respiratory Health Survey (ECRHS). Data were available for 7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and 1210 with current asthma). Associations between occupational exposure to specific asthmagens and asthma control status (33% with uncontrolled asthma, based on the Global Initiative for Asthma guidelines) were evaluated using logistic and multinomial regressions, adjusted for age, sex and smoking status, with study areas included as a random effect. Statistically significant positive associations were observed between uncontrolled adult-onset asthma and both past 12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6 (1.0-2.40) and 1.7 (1.2-2.5), respectively); high (1.7 (1.0-2.8) and 1.9 (1.3-2.9), respectively) and low (1.6 (1.0-2.7) and 1.8 (1.2-2.7), respectively) molecular weight agents; and cleaning agents (2.0 (1.1-3.6) and 2.3 (1.4-3.6), respectively), with stronger associations for long-term exposures. These associations were mainly explained by the exacerbation domain of asthma control and no associations were observed between asthmagens and partly controlled asthma. These findings suggest that occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma. Occupational risk factors should be quickly identified to prevent uncontrolled asthma.
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| 5. |
- Mirabelli, Maria C., et al.
(författare)
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Metalworking exposures and persistent skin symptoms in the ECRHS II and SAPALDIA 2 cohorts
- 2009
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 60:5, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diseases of the skin are important and often preventable conditions occurring among workers with dermal exposures to irritant and sensitizing agents. OBJECTIVE: We conducted this analysis to assess the associations between metalworking exposures and current and persistent skin symptoms among male and female participants in two population-based epidemiologic studies. METHODS: We pooled data from the European Community Respiratory Health Survey II (ECRHS II) and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults 2 (SAPALDIA 2), two prospective cohort studies in Europe. Each participant completed interviewer-administered questionnaires to provide information about symptoms and exposures related to selected occupations, including metalworking, during the follow-up periods. We assessed associations between skin symptoms and the frequency of metalworking exposures among 676 ECRHS II/SAPALDIA 2 respondents. RESULTS: Current skin symptoms were reported by 10% of metalworkers and were associated with frequent use, defined as four or more days per week, of oil-based metalworking fluids [prevalence ratio (PR): 1.76, 95% confidence interval (CI): 1.25-2.49)] and organic solvent/degreasing agents (PR: 2.06, 95% CI: 1.21-3.50). CONCLUSIONS: Skin symptom prevalence is associated with increasing frequency of oil-based metalworking fluid and degreasing agent use. Our findings justify assessing strategies for reducing the frequency of metal-related exposures.
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| 6. |
- Mirabelli, Maria C, et al.
(författare)
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Occupational risk factors for asthma among nurses and related healthcare professionals in an international study
- 2007
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 64:7, s. 474-479
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The authors examined the relations between self-reported work tasks, use of cleaning products and latex glove use with new-onset asthma among nurses and other healthcare workers in the European Community Respiratory Health Survey (ECRHS II). Methods: In a random population sample of adults from 22 European sites, 332 participants reported working in nursing and other related healthcare jobs during the nine-year ECRHS II follow-up period and responded to a supplemental questionnaire about their principal work settings, occupational tasks, products used at work and respiratory symptoms. Poisson regression models with robust error variances were used to compare the risk of new-onset asthma among healthcare workers with each exposure to that of respondents who reported professional or administrative occupations during the entire follow-up period (n=2481). Results: Twenty (6%) healthcare workers and 131 (5%) members of the referent population reported new-onset asthma. Compared to the referent group, the authors observed increased risks among hospital technicians (RR 4.63; 95% Cl 1.87 to 11.5) and among those using ammonia and/or bleach at work (RR 2.16; 95% Cl 1.03 to 4.53). Conclusions: In the ECRHS II cohort, hospital technicians and other healthcare workers experience increased risks of new-onset current asthma, possibly due to specific products used at work.
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| 7. |
- 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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| 8. |
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| 9. |
- Zock, Jan-Paul, et al.
(författare)
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Domestic use of hypochlorite bleach, atopic sensitization, and respiratory symptoms in adults
- 2009
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 124:4, s. 731-738
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Professional use of hypochlorite (bleach) has been associated with respiratory symptoms. Bleach is capable of inactivating allergens, and there are indications that its domestic use may reduce the risk of allergies in children. OBJECTIVE: To study the associations between household use of bleach and atopic sensitization, allergic diseases, and respiratory health status in adults. METHODS: We identified 3626 participants of the European Community Respiratory Health Survey II in 10 countries who did the cleaning in their homes and for whom data on specific serum IgE to 4 environmental allergens were available. Frequency of bleach use and information on respiratory symptoms were obtained in face-to-face interviews. House dust mite and cat allergens in mattress dust were measured in a subsample. Associations between the frequency of bleach use and health outcomes were evaluated by using multivariable mixed logistic regression analyses. RESULTS: The use of bleach was associated with less atopic sensitization (odds ratio [OR], 0.75; 95% CI, 0.63-0.89). This association was apparent for specific IgE to both indoor (cat) and outdoor (grass) allergens, and was consistent in various subgroups, including those without any history of respiratory problems (OR, 0.85). Dose-response relationships (P < .05) were apparent for the frequency of bleach use and sensitization rates. Lower respiratory tract symptoms, but not allergic symptoms, were more prevalent among those using bleach 4 or more days per week (OR, 1.24-1.49). The use of bleach was not associated with indoor allergen concentrations. CONCLUSION: People who clean their homes with hypochlorite bleach are less likely to be atopic but more likely to have respiratory symptoms.
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| 10. |
- Zock, Jan-Paul, et al.
(författare)
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The use of household cleaning sprays and adult asthma : an international longitudinal study
- 2007
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 176:8, s. 735-741
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Cleaning work and professional use of certain cleaning products have been associated with asthma, but respiratory effects of nonprofessional home cleaning have rarely been studied. Objectives: To investigate the risk of new-onset asthma in relation to the use of common household cleaners. Methods: Within the follow-up of the European Community Respiratory Health Survey in 10 countries, we identified 3,503 persons doing the cleaning in their homes and who were free of asthma at baseline. Frequency of use of 15 types of cleaning products was obtained in a face-to-face interview at follow-up. We studied the incidence of asthma defined as physician diagnosis and as symptoms or medication usage at follow-up. Associations between asthma and the use of cleaning products were evaluated using multivariable Cox proportional hazards or log-binomial regression analysis. Measurements and Main Results: The use of cleaning sprays at least weekly (42% of participants) was associated with the incidence of asthma symptoms or medication (relative risk [RR], 1.49; 95% confidence interval [Cl], 1.12-1.99) and wheeze (RR, 1.39; 95% Cl, 1.06-1.80). The incidence of physician-diagnosed asthma was higher among those using sprays at least 4 days per week (RR, 2.11; 95% Cl, 1.15-3.89). These associations were consistent for subgroups and not modified by atopy. Dose-response relationships (P < 0.05) were apparent for the frequency of use and the number of different sprays. Risks were predominantly found for the commonly used glass-cleaning, furniture, and air-refreshing sprays. Cleaning products not applied in spray form were not associated with asthma. Conclusions: Frequent use of common household cleaning sprays may be an important risk factor for adult asthma.
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