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Sökning: WFRF:(Lebedeva N. V.)

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  • Pulit, S. L., et al. (författare)
  • Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
  • 2018
  • Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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  • Patel, Y., et al. (författare)
  • Virtual Ontogeny of Cortical Growth Preceding Mental Illness
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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  • Marini, S., et al. (författare)
  • Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
  • 2019
  • Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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  • Kurbanov, R.N., et al. (författare)
  • A detailed luminescence chronology of the Lower Volga loess-palaeosol sequence at Leninsk
  • 2022
  • Ingår i: Quaternary Geochronology. - : Elsevier. - 1871-1014 .- 1878-0350. ; 73
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a detailed luminescence chronology of the loess-palaeosol sequences in the Lower Volga region of Russia at the Leninsk site – an important palaeogeographic archive describing the climate and environmental conditions of regressive stages of the Caspian Sea. The chronology of these sediments has received very little attention compared to the under- and overlying marine deposits. The degree of bleaching was addressed by making use of the differential resetting rates of quartz and feldspar. Our results show that the quartz OSL and feldspar pIRIR50,290 signals were sufficiently bleached before deposition and uncertainties in bleaching have a negligible impact on the reliability of the luminescence ages. The combined quartz OSL and K-feldspar pIRIR50,290 chronology constrains the main stages of the Northern Caspian Lowland evolution during the Late Quaternary. During early MIS 5 (130–120 ka), the northern part of the Lower Volga was covered by a shallow brackish water estuary of the warm Late Khazarian Caspian Sea transgression. After ∼122 ka, the Volga incised the Northern Caspian Lowland surface following sea-level decrease and the start of subaerial conditions at Leninsk. Loess accumulation rate increased towards the end of MIS 5 and two palaeosols of presumably MIS 5с and MIS 5a age formed, exhibiting features evidencing a dry, cold climate, influenced by long seasonal flooding by the Volga River. Cryogenesis affecting the MIS 5a soil is a regional phenomenon and is dated to between ∼70 and 90 ka. The overlying thick Atelian loess unit formed during the cold periods of MIS 4 and MIS 3. Clear erosional features at the top of the Atelian loess are constrained by luminescence to ∼35 to ∼24 ka, allowing reconstruction of erosion of 150–200 cm of loess.
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  • Milfont, T. L., et al. (författare)
  • On the Relation Between Social Dominance Orientation and Environmentalism: A 25-Nation Study
  • 2018
  • Ingår i: Social Psychological and Personality Science. - : SAGE Publications. - 1948-5506 .- 1948-5514. ; 9:7, s. 802-814
  • Tidskriftsartikel (refereegranskat)abstract
    • Approval of hierarchy and inequality in society indexed by social dominance orientation (SDO) extends to support for human dominance over the natural world. We tested this negative association between SDO and environmentalism and the validity of the new Short Social Dominance Orientation Scale in two cross-cultural samples of students (N = 4,163, k = 25) and the general population (N = 1,237, k = 10). As expected, the higher people were on SDO, the less likely they were to engage in environmental citizenship actions, pro-environmental behaviors and to donate to an environmental organization. Multilevel moderation results showed that the SDO-environmentalism relation was stronger in societies with marked societal inequality, lack of societal development, and environmental standards. The results highlight the interplay between individual psychological orientations and social context, as well as the view of nature subscribed to by those high in SDO.
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