| 1. |
- Savage, J. E., et al.
(författare)
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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:7, s. 912-919
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Tidskriftsartikel (refereegranskat)abstract
- Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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| 2. |
- Heikkila, Katriina, et al.
(författare)
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Long working hours and cancer risk : a multi-cohort study
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 114, s. 813-818
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Working longer than the maximum recommended hours is associated with an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer is unclear.METHODS: This multi-cohort study examined the association between working hours and cancer risk in 116 462 men and women who were free of cancer at baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers; weekly working hours were self-reported.RESULTS: During median follow-up of 10.8 years, 4371 participants developed cancer (n colorectal cancer: 393; n lung cancer: 247; n breast cancer: 833; and n prostate cancer: 534). We found no clear evidence for an association between working hours and the overall cancer risk. Working hours were also unrelated the risk of incident colorectal, lung or prostate cancers. Working ⩾55 h per week was associated with 1.60-fold (95% confidence interval 1.12-2.29) increase in female breast cancer risk independently of age, socioeconomic position, shift- and night-time work and lifestyle factors, but this observation may have been influenced by residual confounding from parity.CONCLUSIONS: Our findings suggest that working long hours is unrelated to the overall cancer risk or the risk of lung, colorectal or prostate cancers. The observed association with breast cancer would warrant further research.
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| 3. |
- Virtanen, Marianna, et al.
(författare)
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Long working hours and alcohol use : systematic review and meta-analysis of published studies and unpublished individual participant data.
- 2015
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833 .- 0959-8138. ; 350, s. Art. no. g7772-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To quantify the association between long working hours and alcohol use.DESIGN: Systematic review and meta-analysis of published studies and unpublished individual participant data.DATA SOURCES: A systematic search of PubMed and Embase databases in April 2014 for published studies, supplemented with manual searches. Unpublished individual participant data were obtained from 27 additional studies.REVIEW METHODS: The search strategy was designed to retrieve cross sectional and prospective studies of the association between long working hours and alcohol use. Summary estimates were obtained with random effects meta-analysis. Sources of heterogeneity were examined with meta-regression.RESULTS: Cross sectional analysis was based on 61 studies representing 333 693 participants from 14 countries. Prospective analysis was based on 20 studies representing 100 602 participants from nine countries. The pooled maximum adjusted odds ratio for the association between long working hours and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross sectional analysis of published and unpublished data. Odds ratio of new onset risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective published and unpublished data. In the 18 studies with individual participant data it was possible to assess the European Union Working Time Directive, which recommends an upper limit of 48 hours a week. Odds ratios of new onset risky alcohol use for those working 49-54 hours and ≥55 hours a week were 1.13 (1.02 to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01 to 1.25; adjusted difference in incidence 0.7 percentage points), respectively, compared with working standard 35-40 hours (incidence of new onset risky alcohol use 6.2%). There was no difference in these associations between men and women or by age or socioeconomic groups, geographical regions, sample type (population based v occupational cohort), prevalence of risky alcohol use in the cohort, or sample attrition rate.CONCLUSIONS: Individuals whose working hours exceed standard recommendations are more likely to increase their alcohol use to levels that pose a health risk.
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| 4. |
- Virtanen, Marianna, et al.
(författare)
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Perceived job insecurity as a risk factor for incident coronary heart disease : systematic review and meta-analysis
- 2013
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Ingår i: The BMJ. - : BMJ. - 1756-1833. ; 347
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the association between self reported job insecurity and incident coronary heart disease.Design A meta-analysis combining individual level data from a collaborative consortium and published studies identified by a systematic review.Data sources We obtained individual level data from 13 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. Four published prospective cohort studies were identified by searches of Medline (to August 2012) and Embase databases (to October 2012), supplemented by manual searches.Review methods Prospective cohort studies that reported risk estimates for clinically verified incident coronary heart disease by the level of self reported job insecurity. Two independent reviewers extracted published data. Summary estimates of association were obtained using random effects models.Results The literature search yielded four cohort studies. Together with 13 cohort studies with individual participant data, the meta-analysis comprised up to 174 438 participants with a mean follow-up of 9.7 years and 1892 incident cases of coronary heart disease. Age adjusted relative risk of high versus low job insecurity was 1.32 (95% confidence interval 1.09 to 1.59). The relative risk of job insecurity adjusted for sociodemographic and risk factors was 1.19 (1.00 to 1.42). There was no evidence of significant differences in this association by sex, age (<50 v >= 50 years), national unemployment rate, welfare regime, or job insecurity measure.Conclusions The modest association between perceived job insecurity and incident coronary heart disease is partly attributable to poorer socioeconomic circumstances and less favourable risk factor profiles among people with job insecurity.
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| 5. |
- Kivimäki, Mika, et al.
(författare)
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Long working hours and risk of coronary heart disease and stroke : a systematic review and meta-analysis of published and unpublished data for 603 838 individuals
- 2015
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Ingår i: The Lancet. - : The Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 386:10005, s. 1739-1746
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Tidskriftsartikel (refereegranskat)abstract
- Background Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. Methods We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. Findings We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603 838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528 908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5.1 million person-years (mean 8.5 years), in which 4768 events were recorded, and for stroke was 3.8 million person-years (mean 7.2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (>= 55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1.13, 95% CI 1.02-1.26; p=0.02) and incident stroke (1.33, 1.11-1.61; p=0.002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1.30-1.42). We recorded a dose-response association for stroke, with RR estimates of 1.10 (95% CI 0.94-1.28; p=0.24) for 41-48 working hours, 1.27 (1.03-1.56; p=0.03) for 49-54 working hours, and 1.33 (1.11-1.61; p=0.002) for 55 working hours or more per week compared with standard working hours (p(trend)<0.0001). Interpretation Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours.
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| 6. |
- Theorell, Töres, et al.
(författare)
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Job strain and cardiovascular disease risk factors : Meta-analysis of individual-participant data from 47,000 men and women
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6, s. e67323-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundJob strain is associated with an increased coronary heart disease risk, but few large-scale studies have examined the relationship of this psychosocial characteristic with the biological risk factors that potentially mediate the job strain – heart disease association.Methodology and Principal FindingsWe pooled cross-sectional, individual-level data from eight studies comprising 47,045 participants to investigate the association between job strain and the following cardiovascular disease risk factors: diabetes, blood pressure, pulse pressure, lipid fractions, smoking, alcohol consumption, physical inactivity, obesity, and overall cardiovascular disease risk as indexed by the Framingham Risk Score. In age-, sex-, and socioeconomic status-adjusted analyses, compared to those without job strain, people with job strain were more likely to have diabetes (odds ratio 1.29; 95% CI: 1.11–1.51), to smoke (1.14; 1.08–1.20), to be physically inactive (1.34; 1.26–1.41), and to be obese (1.12; 1.04–1.20). The association between job strain and elevated Framingham risk score (1.13; 1.03–1.25) was attributable to the higher prevalence of diabetes, smoking and physical inactivity among those reporting job strain.ConclusionsIn this meta-analysis of work-related stress and cardiovascular disease risk factors, job strain was linked to adverse lifestyle and diabetes. No association was observed between job strain, clinic blood pressure or blood lipids.
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