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Sökning: WFRF:(Rantanen Taina)

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  • Albrecht, Eva, et al. (författare)
  • Telomere length in circulating leukocytes is associated with lung function and disease
  • 2014
  • Ingår i: European Respiratory Journal. - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.</p>
  • Artigas Soler, María, et al. (författare)
  • Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
  • 2011
  • Ingår i: Nature genetics. - 1546-1718. ; 43:11, s. 1082-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
  • Demirkan, Ayse, et al. (författare)
  • Genetic architecture of circulating lipid levels
  • 2011
  • Ingår i: European Journal of Human Genetics. - 1018-4813 .- 1476-5438. ; 19:7, s. 813-819
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.</p>
  • Jackson, Victoria E, et al. (författare)
  • Meta-analysis of exome array data identifies six novel genetic loci for lung function.
  • 2018
  • Ingår i: Wellcome open research. - 2398-502X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background:</strong> Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. <strong>Methods:</strong> We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV <sub>1</sub>), forced vital capacity (FVC) and the ratio of FEV <sub>1</sub> to FVC (FEV <sub>1</sub>/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. <strong>Results:</strong> We identified significant (P&lt;2·8x10 <sup>-7</sup>) associations with six SNPs: a nonsynonymous variant in <em>RPAP1</em>, which is predicted to be damaging, three intronic SNPs ( <em>SEC24C, CASC17</em> and <em>UQCC1</em>) and two intergenic SNPs near to <em>LY86</em> and <em>FGF10.</em> Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including <em>TYRO3</em> and <em>PLAU</em>. <strong>Conclusions:</strong> Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.</p>
  • Kulmala, Jenni, et al. (författare)
  • Association between mid- to late life physical fitness and dementia: evidence from the CAIDE study
  • 2014
  • Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 276:3, s. 296-307
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Objectives</strong></p><p>This study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid- to late life, and dementia risk.</p><p><strong>Design</strong></p><p>Prospective cohort study.</p><p><strong>Setting</strong></p><p>Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) study.</p><p><strong>Subjects</strong></p><p>Subjects were selected from four independent, random samples of population-based cardiovascular surveys and were first examined in 1972, 1977, 1982, or 1987, when they were on average 50 years old. The CAIDE target population included 3,559 individuals. A random sample of 2,000 individuals still alive in 1997 was drawn for re-examinations (performed in 1998 and 2005–2008) that consisted of cognitive assessments, with 1,511 subjects participating in at least one re-examination. Dementia diagnoses were also confirmed from national registers for the entire target population.</p><p><strong>Main outcome measure</strong></p><p>All-cause dementia.</p><p><strong>Results</strong></p><p>Poor physical fitness at midlife was associated with increased dementia risk in the entire target population [hazard ratio (HR), 1.5; 95% confidence interval (CI), 1.1–2.0]. In participants, odds ratio (OR) was 2.0 (95% CI, 0.9–4.0). This association was significant in <em>apolipoprotein E</em> ε<em>4</em> allele (<em>APOE</em>ε<em>4</em>) non-carriers (OR, 4.3; 95% CI, 1.4–13.3), men (HR, 1.8; 95% CI, 1.1–3.0), and people with chronic conditions (HR, 2.9; 95% CI, 1.3–6.6). A decline in fitness after midlife was also associated with dementia (OR, 3.0; 95% CI, 1.7–5.1), which was significant among both men and women and more pronounced in <em>APOE</em>ε<em>4</em> carriers (OR, 4.4; 95% CI, 2.1–9.1).</p><p><strong>Conclusions</strong></p><p>Perceived poor physical fitness reflects a combination of biological and lifestyle-related factors that can increase dementia risk. A simple question about perceived physical fitness may reveal at-risk individuals who could benefit from preventive interventions.</p>
  • Obeidat, Ma'en, et al. (författare)
  • A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample
  • 2011
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 6:5, s. e19382
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Rationale: </strong></p> <p>Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium).</p> <p><strong>Objectives:</strong></p> <p>To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample.</p> <p><strong>Methods:</strong></p> <p>We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations.</p> <p><strong>Results:</strong></p> <p>The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers.</p> <p><strong>Conclusions: </strong></p> <p>Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.</p>
  • Portegijs, Erja, et al. (författare)
  • Perceived and objective entrance-related environmental barriers and daily out-of-home mobility in community-dwelling older people
  • 2017
  • Ingår i: Archives of Gerontology and Geriatrics. - Elsevier. - 0167-4943. ; 69, s. 69-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose We studied whether entrance-related environmental barriers, perceived and objectively recorded, were associated with moving out-of-home daily in older people with and without limitations in lower extremity performance. Methods Cross-sectional analyses of the “Life-space mobility in old age” cohort including 848 community-dwelling 75–90-year-old of central Finland. Participants reported their frequency of moving out-of-home (daily vs. 0–6 times/week) and perceived entrance-related environmental barriers (yes/no). Lower extremity performance was assessed (Short Physical Performance Battery) and categorized as poorer (score 0–9) or good (score 10–12). Environmental barriers at entrances and in exterior surroundings were objectively registered (Housing Enabler screening tool) and divided into tertiles. Logistic regression analyses were adjusted for age, sex, number of chronic diseases, cognitive function, month of assessment, type of neighborhood, and years lived in the current home. Results At home entrances a median of 6 and in the exterior surroundings 5 environmental barriers were objectively recorded, and 20% of the participants perceived entrance-related barriers. The odds for moving out-of-home less than daily increased when participants perceived entrance-related barrier(s) or when they lived in homes with higher numbers of objectively recorded environmental barriers at entrances. Participants with limitations in lower extremity performance were more susceptible to these environmental barriers. Objectively recorded environmental barriers in the exterior surroundings did not compromise out-of-home mobility. Conclusion Entrance-related environmental barriers may hinder community-dwelling older people to move out-of-home daily especially when their functional capacity is compromised. Potentially, reducing entrance-related barriers may help to prevent confinement to the home.
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