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  • Lumbers, R. T., et al. (författare)
  • The genomics of heart failure: design and rationale of the HERMES consortium
  • 2021
  • Ingår i: Esc Heart Failure. - : John Wiley & Sons, Ltd. - 2055-5822. ; 8:6, s. 5531-5541
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
  • Shah, Sonia, et al. (författare)
  • Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
  • 2020
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723 .- 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
  • Eriksson, Kimmo, et al. (författare)
  • Perceptions of the appropriate response to norm violation in 57 societies
  • 2021
  • Ingår i: Nature Communications. - : Nature Research. - 2041-1723 .- 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about peoples preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in peoples perception of the appropriateness of norm violations.
  • Wang, R., et al. (författare)
  • Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age? : A population-based study
  • 2014
  • Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 21:8, s. 1076-1082
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-epsilon 4 allele. Methods: This population-based study included 492 participants (age >= 60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models. Results: More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-epsilon 4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-epsilon 4 had no influential effect. Conclusion: The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-epsilon 4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.
  • Qiu, C., et al. (författare)
  • Medial temporal lobe is vulnerable to vascular risk factors in men : a population based study
  • 2012
  • Ingår i: European Journal of Neurology. - 1351-5101 .- 1468-1331. ; 19:6, s. 876-883
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Vascular risk factors (VRFs) are known to cause cerebral microvascular disease, but evidence supporting an effect of VRFs on regional brain atrophy is mixed. We investigate whether an aggregation of VRFs is associated with volume of hippocampus and entorhinal cortex in elderly people living in the community. Methods: This cross-sectional study consists of 523 participants (age =60 years, 59.3% women) of the SNAC-K Study in central Stockholm, Sweden, who were free of clinical stroke and cognitive impairment. We collected data on VRFs through interviews, clinical examination and inpatient register system. Hippocampal and entorhinal cortex volume was manually measured on magnetic resonance images. Data were analysed with general linear regression models controlling for demographics and total intracranial volume. Results: In men, high total cholesterol and diabetes were significantly or marginally associated with smaller hippocampus and entorhinal cortex; when current smoking, binge alcohol drinking, high cholesterol and diabetes were aggregated, an increasing number of VRFs were significantly associated with decreasing volume of hippocampus and entorhinal cortex (P for linear trend <0.01). In women, none of individual VRFs or their aggregation was significantly associated with the volume of these brain regions, except former smoking that was significantly associated with a larger volume of these regions. Conclusions: Aggregation of VRFs is associated with reduced hippocampal and entorhinal cortex volume in apparently healthy elderly men, but not in women. This implies that in men, the medial temporal lobe is vulnerable to cardiovascular risk factors.
  • Gerritsen, L., et al. (författare)
  • The influence of negative life events on hippocampal and amygdala volumes in old age : a life-course perspective
  • 2014
  • Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 45:6, s. 1219-1228
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults.METHOD: In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning.RESULTS: Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women.CONCLUSIONS: These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.
  • Hedman, L., et al. (författare)
  • Association of Electronic Cigarette Use With Smoking Habits, Demographic Factors, and Respiratory Symptoms
  • 2018
  • Ingår i: Jama Network Open. - : American Medical Association. - 2574-3805. ; 1:3
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE There is an ongoing debate about whether electronic cigarettes (e-cigarettes) are the solution to the tobacco epidemic or a new public health threat. Large representative studies are needed to study e-cigarette use in the general population, but hardly any have been published. OBJECTIVES To estimate the prevalence of e-cigarette use and to investigate the association of e-cigarette use with smoking habits, demographic factors, and respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional, population-based study of random samples of the population, performed within the Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). The same validated questionnaire including identical questions was used in OLIN and WSAS. In 2016, OLIN and WSAS conducted postal questionnaire surveys in random samples of adults aged 20 to 75 years. In OLIN, 6519 participated (response rate, 56.4%); in WSAS, 23 753 participated (response rate, 50.1%). MAIN OUTCOMES AND MEASURES Electronic cigarette use, smoking habits, and respiratory symptoms. RESULTS Of 30 272 participants (16 325 women [53.9%]). 3897 (12.9%) were aged 20 to 29 years; 4242 (14.0%). 30 to 39 years; 5082 (16.8%). 40 to 49 years; 6052 (20.0%), 50 to 59 years; 6628 (21.9%), 60 to 69 years; and 4371(14.4%), 70 to 75 years. The number of current smokers was 3694 (12.3%), and 7305 (24.4%) were former smokers. The number of e-cigarette users was 529 (2.0%). and e-cigarette use was more common among men (275 of 12 347 [2.2%; 95% CI, 2.0%-2.5%]) than women (254 of 14 022 [1.8%; 95% CI, 1.6%-2.0%]). Among current smokers. 350 of 3566 (9.8%; 95% CI, 8.8%10.8%) used e-cigarettes compared with 79 of 6875 (1.1%; 95% CI, 0.9%-1.3%) in former smokers and 96 of 15 832 (0.6%; 95% CI, 0.5%-0.7%) in nonsmokers (P < .001). Among e-cigarette users who answered the survey question about cigarette-smoking habits (n = 525). 350 (66.7%; 95% CI, 62.7%-70.7%) were current smokers, 79 (15.0%; 95% CI, 11.9%-18.1%) were former smokers, and 96 (18.3%; 95% CI, 15.0%-21.6%) were nonsmokers (P < .001 for trend). In a regression analysis, e-cigarette use was associated with male sex (odds ratio [OR], 1.35; 95% CI. 1.12-1.62); age groups 20 to 29 years (OR. 2.77; 95% CI, 1.90-4.05), 30 to 39 years (OR, 2.27; 95% CI, 1.53-3.36), 40 to 49 years (OR, 1.65; 95% CI, 1.11-2.44). and 50 to 59 years (OR, 1.47; 95% CI, 1.01-2.12); educational level at primary school (OR, 1.99; 95% CI, 1.51-2.64) and upper secondary school (OR, 1.57; 95% CI, 1.25-1.96); former smoking (OR. 2.37; 95% CI, 1.73-3.24); and current smoking (OR. 18.10; 95% CI, 14.19-23.09). All respiratory symptoms were most common among dual users and former smokers and nonsmokers who used e-cigarettes. CONCLUSIONS AND RELEVANCE Use of e-cigarettes was most common among smokers, and dual users had the highest prevalence of respiratory symptoms. On a population level, this study indicates that the present use of e-cigarettes does not adequately serve as a smoking cessation tool.
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