ORCID Profile
0000-0001-8611-1630
Current Organisation
Friedrich Schiller University Jena
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2015
DOI: 10.1161/STROKEAHA.115.009252
Abstract: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance ( P ×10 −8 ). Four loci were suggestive ( P ×10 −5 ) of an association with WML progression: 10q24.32 (rs10883817, P =1.46×10 −6 ) 12q13.13 (rs4761974, P =8.71×10 −7 ) 20p12.1 (rs6135309, P =3.69×10 −6 ) and 4p15.31 (rs7664442, P =2.26×10 −6 ). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden. Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.
Publisher: Elsevier BV
Date: 06-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-07-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
DOI: 10.1212/WNL.0000000000006037
Abstract: To assess putative risk factors and outcome of multiple and early recurrent cervical artery dissection (CeAD). We combined data from 2 multicenter cohorts and compared patients with multiple CeAD at initial diagnosis, early recurrent CeAD within 3 to 6 months, and single nonrecurrent CeAD. Putative risk factors, clinical characteristics, functional outcome, and risk of recurrent ischemic events were assessed. Of 1,958 patients with CeAD (mean ± SD age 44.3 ± 10 years, 43.9% women), 1,588 (81.1%) had single nonrecurrent CeAD, 340 (17.4%) had multiple CeAD, and 30 (1.5%) presented with single CeAD at admission and had early recurrent CeAD. Patients with multiple or early recurrent CeAD did not significantly differ with respect to putative risk factors, clinical presentation, and outcome. In multivariable analyses, patients with multiple or early recurrent CeAD more often had recent infection (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.29–2.53), vertebral artery dissection (OR 1.82, 95% CI 1.34–2.46), family history of stroke (OR 1.55, 95% CI 1.06–2.25), cervical pain (OR 1.36, 95% CI 1.01–1.84), and subarachnoid hemorrhage (OR 2.85, 95% CI 1.01–8.04) at initial presentation compared to patients with single nonrecurrent CeAD. Patients with multiple or early recurrent CeAD also had a higher incidence of cerebral ischemia (hazard ratio 2.77, 95% CI 1.49–5.14) at 3 to 6 months but no difference in functional outcome compared to patients with single nonrecurrent CeAD. Patients with multiple and early recurrent CeAD share similar risk factors, clinical characteristics, and functional outcome. Compared to patients with single nonrecurrent CeAD, they are more likely to have recurrent cerebral ischemia at 3 to 6 months, possibly reflecting an underlying transient vasculopathy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-10-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-01-2019
DOI: 10.1212/WNL.0000000000006851
Abstract: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. We 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. The 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 × 10 −8 and LINC00539/ZDHHC20, p = 5.82 × 10 −9 . Both have been associated with blood pressure (BP)–related phenotypes, but did not replicate in the smaller follow-up s le 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 × 10 −25 p [SSBI] = 5.23 × 10 −14 for hypertension), smoking ( p [BI] = 4.4 × 10 −10 p [SSBI] = 1.2 × 10 −4 ), diabetes ( p [BI] = 1.7 × 10 −8 p [SSBI] = 2.8 × 10 −3 ), previous cardiovascular disease ( p [BI] = 1.0 × 10 −18 p [SSBI] = 2.3 × 10 −7 ), stroke ( p [BI] = 3.9 × 10 −69 p [SSBI] = 3.2 × 10 −24 ), and MRI-defined white matter hyperintensity burden ( p [BI] = 1.43 × 10 −157 p [SSBI] = 3.16 × 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. In 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.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2020
DOI: 10.1038/S41467-020-19111-2
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older in iduals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk in iduals and for genetically-informed prioritization of drug targets for prevention trials.
Publisher: Wiley
Date: 31-10-2021
Abstract: Plant damage by invertebrate herbivores and pathogens influences the dynamics of grassland ecosystems, but anthropogenic changes in nitrogen and phosphorus availability can modify these relationships. Using a globally distributed experiment, we describe leaf damage on 153 plant taxa from 27 grasslands worldwide, under ambient conditions and with experimentally elevated nitrogen and phosphorus. Invertebrate damage significantly increased with nitrogen addition, especially in grasses and non‐leguminous forbs. Pathogen damage increased with nitrogen in grasses and legumes but not forbs. Effects of phosphorus were generally weaker. Damage was higher in grasslands with more precipitation, but climatic conditions did not change effects of nutrients on leaf damage. On average, invertebrate damage was relatively higher on legumes and pathogen damage was relatively higher on grasses. Community‐weighted mean damage reflected these functional group patterns, with no effects of N on community‐weighted pathogen damage (due to opposing responses of grasses and forbs) but stronger effects of N on community‐weighted invertebrate damage (due to consistent responses of grasses and forbs). Synthesis . As human‐induced inputs of nitrogen and phosphorus continue to increase, understanding their impacts on invertebrate and pathogen damage becomes increasingly important. Our results demonstrate that eutrophication frequently increases plant damage and that damage increases with precipitation across a wide array of grasslands. Invertebrate and pathogen damage in grasslands is likely to increase in the future, with potential consequences for plant, invertebrate and pathogen communities, as well as the transfer of energy and nutrients across trophic levels.
No related grants have been discovered for Sabrina Lémeret.