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- Chauhan, G., et al.
(author)
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Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
- 2019
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5
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Journal article (peer-reviewed)abstract
- ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 10(-9). Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p([BI]) = 9.38 x 10(-25); p([SSBI]) = 5.23 x 10(-14) for hypertension), smoking (p([BI]) = 4.4 x 10(-10); p([SSBI]) = 1.2 x 10(-4)), diabetes (p([BI]) = 1.7 x 10(-8); p([SSBI]) = 2.8 x 10(-3)), previous cardiovascular disease (p([BI]) = 1.0 x 10(-18); p([SSBI]) = 2.3 x 10(-7)), stroke (p([BI]) = 3.9 x 10(-69); p([SSBI]) = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p([BI]) = 1.43 x 10(-157); p([SSBI]) = 3.16 x 10(-106)), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
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| 2. |
- Valdes-Marquez, E., et al.
(author)
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Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study
- 2019
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:11
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Journal article (peer-reviewed)abstract
- Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 x 10(-8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 x 10(-3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 x 10(-3)) when compared with that for CHD. In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
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| 7. |
- Casamiquela, L., et al.
(author)
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OCCASO - II. Physical parameters and Fe abundances of red clump stars in 18 open clusters
- 2017
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 470:4, s. 4363-4381
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Journal article (peer-reviewed)abstract
- Open clusters have long been used to study the chemodynamical evolution of the Galactic disc. This requires a homogeneously analysed sample covering a wide range of ages and distances. In this paper, we present the Open Clusters Chemical Abundances from Spanish Observatories (OCCASO) second data release. This comprises a sample of high-resolution (R > 65 000) and high signal-to-noise spectra of 115 red clump stars in 18 open clusters. We derive atmospheric parameters (T-eff, log g, xi), and [Fe/H] abundances using two analysis techniques: equivalent widths and spectral synthesis. A detailed comparison and a critical review of the results of the two methods are made. Both methods are carefully tested between them, with the Gaia FGK benchmark stars, and with an extensive sample of literature values. We perform a membership study using radial velocities and the resulting abundances. Finally, we compare our results with a chemodynamical model of the Milky Way thin disc concluding that the oldest open clusters are consistent with the models only when dynamical effects are taken into account.
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