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Sökning: WFRF:(Buchman Aron S) > Refereegranskat

  • Resultat 1-7 av 7
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  • Lu, Yingchang, et al. (författare)
  • New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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  • Ben-Avraham, Dan, et al. (författare)
  • The complex genetics of gait speed : Genome-wide meta-analysis approach
  • 2017
  • Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 9:1, s. 209-246
  • Tidskriftsartikel (refereegranskat)abstract
    • Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.
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5.
  • Song, Ruixue, et al. (författare)
  • Associations Between Cardiovascular Risk, Structural Brain Changes, and Cognitive Decline
  • 2020
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 75:20, s. 2525-2534
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear. OBJECTIVES This study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences. METHODS Within the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models. RESULTS In all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 +/- 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (beta = -0.019; 95% confidence interval [CI]: -0.035 to -0.003), episodic memory (beta = -0.023; 95% CI: -0.041 to -0.004), working memory (beta = -0.021; 95% CI: -0.035 to -0.007), and perceptual speed (beta = -0.027; 95% CI: -0.042 to -0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (beta = -0.021; 95% CI: -0.042 to -0.000), gray matter (beta = -1.569; 95% CI: -2.757 to -0.382), and total brain (beta = -1.588; 95% CI: -2.832 to -0.344), and greater volume of white matter hyperintensities (beta = 0.035; 95% CI: 0.001 to 0.069). CONCLUSIONS Higher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.
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  • Song, Ruixue, et al. (författare)
  • Association of cardiovascular risk burden with risk of dementia and brain pathologies : A population-based cohort study
  • 2021
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:12, s. 1914-1922
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies. Methods Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies. Results The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12). Conclusions A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.
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7.
  • Wang, Zhangyu, et al. (författare)
  • Influence of Cardiovascular Risk Burden on Motor Function Among Older Adults : Mediating Role of Cardiovascular Diseases Accumulation and Cognitive Decline
  • 2022
  • Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: This study aimed to investigate the association of the cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) with the trajectories of motor function over time and to assess the mediating effects of cardiovascular diseases (CVDs) accumulation and cognitive decline in such association.Methods: In Rush Memory and Aging Project, a total of 1,378 physical health participants (mean age: 79.3 ± 7.3 years) were followed up for up to 22 years. FGCRS at baseline was assessed and categorized into tertiles (lowest, middle, and highest). Global motor function (including dexterity, gait, and hand strength) was assessed annually with 10 motor tests. CVDs (including stroke, congestive heart failure, and other heart diseases) were ascertained at baseline and follow-ups, and the number of CVDs accumulation over time was assessed. Global cognitive function was tested annually by 19 tests. Data were analyzed using the linear mixed-effects models and mediation analysis.Results: At baseline, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Over the follow-up (median: 5.3 years; interquartile range: 2.9–9.0 years), in multi-adjusted mixed-effects models, the highest FGCRS was associated with faster decline in global motor function (β = −0.0038; 95% confidence interval [CI]: −0.0069 to −0.0008), dexterity (β = −0.0056; 95% CI: −0.0093 to −0.0020), gait (β = −0.0039; 95% CI: −0.0077 to −0.0001), and hand strength (β = −0.0053; 95% CI: −0.0098 to −0.0008) compared with the lowest tertile. In mediation analysis, CVDs accumulation and cognitive decline mediated 8.4% and 42.9% of the association between FGCRS and global motor function over time, respectively.Conclusion: Higher cardiovascular risk burden is associated with a faster decline in motor function including dexterity, gait, and hand strength. CVDs accumulation and cognitive decline may partially mediate the association between cardiovascular risk burden and global motor function decline.
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  • Resultat 1-7 av 7

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