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Träfflista för sökning "WFRF:(Gow Alan J.) "

Sökning: WFRF:(Gow Alan J.)

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1.
  • Wain, Louise V., et al. (författare)
  • Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
  • 2017
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.</p>
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2.
  • Warren, Helen R., et al. (författare)
  • Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 49:3, s. 403-415
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.</p>
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3.
  • Koettgen, Anna, et al. (författare)
  • Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from &gt;140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.</p>
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4.
  • Huffman, Jennifer E., et al. (författare)
  • Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
  • 2015
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.</p>
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5.
  • Bangsbo, Jens, et al. (författare)
  • Copenhagen Consensus statement 2019 physical activity and ageing
  • 2019
  • Ingår i: British Journal of Sports Medicine. - London : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 53:14, s. 856-858
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term ‘older adults’ represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. <em>Physical activity</em> is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. <em>Exercise</em> is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults’ fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual’s physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.</p>
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6.
  • Henning, Georg, et al. (författare)
  • Towards an active and happy retirement? Changes in leisure activity and depressive symptoms during the retirement transition
  • 2020
  • Ingår i: Aging & Mental Health. - Routledge. - 1360-7863 .- 1364-6915.
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objectives: Retirement is a major life transition in the second half of life, and it can be associated with changes in leisure activity engagement. Although theories of retirement adjustment have emphasized the need to find meaningful activities in retirement, little is known about the nature of changes in leisure activity during the retirement transition and their association with mental health.</p><p>Methods: Based on four annual waves of the 'Health, Aging and Retirement Transitions in Sweden' study, we investigated the longitudinal association of leisure activity engagement and depressive symptoms using bivariate dual change score models. We distinguished intellectual, social, and physical activity engagement.</p><p>Results: We found increases in all three domains of activity engagement after retirement. Although level and change of activity and depressive symptoms were negatively associated, the coupling parameters were not significant, thus the direction of effects remains unclear.</p><p>Conclusion: The results highlight the need to consider the role of lifestyle changes for retirement adjustment and mental health.</p>
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7.
  • Henning, Georg, et al. (författare)
  • Towards an active and happy retirement? Changes in leisure activity and depressive symptoms during the retirement transition.
  • 2020
  • Ingår i: Aging & Mental Health. - Routledge. - 1360-7863 .- 1364-6915. ; s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Objectives:</strong> Retirement is a major life transition in the second half of life, and it can be associated with changes in leisure activity engagement. Although theories of retirement adjustment have emphasized the need to find meaningful activities in retirement, little is known about the nature of changes in leisure activity during the retirement transition and their association with mental health.</p><p><strong>Methods:</strong> Based on four annual waves of the 'Health, Aging and Retirement Transitions in Sweden' study, we investigated the longitudinal association of leisure activity engagement and depressive symptoms using bivariate dual change score models. We distinguished intellectual, social, and physical activity engagement.</p><p><strong>Results:</strong> We found increases in all three domains of activity engagement after retirement. Although level and change of activity and depressive symptoms were negatively associated, the coupling parameters were not significant, thus the direction of effects remains unclear.</p><p><strong>Conclusion:</strong> The results highlight the need to consider the role of lifestyle changes for retirement adjustment and mental health.</p>
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8.
  • Henning, Georg, 1989-, et al. (författare)
  • Towards an active and happy retirement? Changes in leisure activity and depressive symptoms during the retirement transition
  • 2020
  • Ingår i: Aging and Mental Health. - 1360-7863 .- 1364-6915.
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Objectives: Retirement is a major life transition in the second half of life, and it can be associated with changes in leisure activity engagement. Although theories of retirement adjustment have emphasized the need to find meaningful activities in retirement, little is known about the nature of changes in leisure activity during the retirement transition and their association with mental health. Methods: Based on four annual waves of the ‘Health, Aging and Retirement Transitions in Sweden’ study, we investigated the longitudinal association of leisure activity engagement and depressive symptoms using bivariate dual change score models. We distinguished intellectual, social, and physical activity engagement. Results: We found increases in all three domains of activity engagement after retirement. Although level and change of activity and depressive symptoms were negatively associated, the coupling parameters were not significant, thus the direction of effects remains unclear. Conclusion: The results highlight the need to consider the role of lifestyle changes for retirement adjustment and mental health.
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