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BACKGROUND: Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease. METHODS: We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757â 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18â 381), cerebral microbleed (3556 cases, 22â 306 controls), white matter perivascular space (9317 cases, 29â 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29â 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29â 708 controls), and lacunar stroke (6030 cases, 248â 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis. RESULTS: We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (ß=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (ß=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (ß=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.
Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Doenças de Pequenos Vasos Cerebrais , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Doenças de Pequenos Vasos Cerebrais/genética , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Hipertensão/tratamento farmacológico , Hipertensão/genética , Feminino , Masculino , Acidente Vascular Cerebral Lacunar/genética , Acidente Vascular Cerebral Lacunar/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Sex difference in the incidence rate of idiopathic pulmonary fibrosis (IPF) indicates that estrogen has a certain protective effect on the disease. Nevertheless, there is a dearth of study investigating the association between factors pertaining to endogenous estrogen exposure level, such as age at menarche (AAM) in women, and IPF. Our study intended to employ Mendelian randomization (MR) method to elucidate the causal association between AAM and IPF. METHODS: Our study utilized AAM as a measure of endogenous estrogen exposure and investigated its causal effect on the risk of IPF through MR. We employed the inverse variance weighted (IVW) method to assess the causal relationship between AAM and IPF risk, with supplementary analyses conducted using the weighted median estimator (WME) and MR-Egger method. Several sensitivity analyses were performed to assess the dependability of MR estimates. RESULTS: A total of 9 selected single nucleotide polymorphisms (SNPs) significantly associated with AAM were selected as instrumental variables. The IVW method showed that genetically later AAM was associated with an increased risk of IPF (odds ratio [OR] = 1.0014, 95%confidence interval [CI] = 1.0005-1.0023, p = 0.001). The median weighting method and the MR-Egger method obtained similar estimates, and no heterogeneity or pleiotropy was found, indicating that the results were robust. CONCLUSIONS: Our MR study suggested a causal relationship between a later onset of menarche and a heightened susceptibility to IPF.
Assuntos
Fibrose Pulmonar Idiopática , Menarca , Humanos , Feminino , Masculino , Menarca/genética , Análise da Randomização Mendeliana , Estrogênios , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/genética , Razão de ChancesRESUMO
PURPOSE OF THE STUDY: Previous studies have established that telomere length is associated with multiple sclerosis (MS). However, confounding factors and reverse causality bias can impair observational research. Here, we conducted a two-sample MR study to see if telomere length is causally linked to MS using publically available GWAS summary statistics. MATERIALS AND METHODS: We screened 13 independent single-nucleotide polymorphisms (SNPs) related to leukocyte telomere length in a recent genome-wide association meta-analysis, which was available for 78,592 samples of European ancestry. The summary statistics for MS were from the latest meta-analyses conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC), which included 115,803 European participants (47,429 MS, 68,374 controls). RESULTS: We found that leukocyte telomere length and MS are correlated (IVW estimate of odds ratio (OR): 2.13 per 1-SD increase in genetically determined telomere length, 95% confidence interval (CI): 1.55-2.92, p = 3.18 × 10-6). CONCLUSION: Our MR study supported that leukocyte telomere length and MS have a positive causal relationship. Further researches are warranted to elucidate the physiological mechanism.
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OBJECTIVE: This study was conducted to examine the relationship among type D personality, acute ischemic stroke (AIS), and white matter hyperintensity (WMH). METHODS: In a cross-sectional study conducted between September 2020 and June 2021, 235 patients aged 50-85 years with first-ever ischemic cerebrovascular disease, including 146 males and 89 females, were enrolled. All participants underwent the Type D Scale-14 test containing negative affectivity (NA) and social inhibition (SI) subscales. Clinical and laboratory data were also collected for analysis. The patients were divided into the AIS group (n = 148) and the transient ischemic attack (TIA) group (n = 87) according to whether there was an acute lesion. RESULTS: Patients with type D personality had a higher frequency of AIS and LAA and a higher level of WMH. Multiple logistic regression showed that the NA score was related to a 1.11-fold increase in the odds of AIS (95% CI: 1.03-1.19). Neither NA nor SI showed a clear association with a higher frequency of LAA. Higher scores of NA (OR = 1.07, 95% CI: 1.01-1.15), SI (OR = 1.11, 95% CI: 1.03-1.19), and the interaction between the two dimensions (OR = 1.03, 95% CI: 1.01-1.05) were independently associated with an increased load of WMH. CONCLUSION: Type D personality was related to AIS and WMH. In particular, it was NA, not SI, affected the occurrence of AIS. Our findings may provide new insights regarding behavioral vulnerability for the development of cerebrovascular disorders.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Personalidade Tipo D , Substância Branca , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Acidente Vascular Cerebral/complicações , Substância Branca/patologiaRESUMO
BACKGROUND: Observational studies suggest that Parkinson's disease (PD) is related with the risk of cardio and cerebrovascular disease. However, the causality is not yet fully established. Therefore, we employed Mendelian randomization to assess whether PD is related to risk of ischemic stroke (IS), IS subtypes, coronary artery disease (CAD) and myocardial infarction (MI). METHODS: Eighty-eight and eleven single nucleotide polymorphisms associated with PD at the genome-wide significance level, were used as instrumental variables for PD in European and East Asian population respectively. Using a 2-sample MR, we examined associations with IS, IS related subtypes, CAD and MI in European population. We also assessed the causal association of PD with IS and CAD in East Asian population. The primary MR analyses were performed by using the random-effects inverse variance weighted approach. RESULTS: In European population, genetic predisposition to PD was related to higher risk of IS (odds ratio [OR], 1.03 per doubling in odds of PD; 95% confidence interval [CI], 1.01-1.05; P = 0.002) and cardioembolic stroke (OR, 1.08 per doubling in odds of PD; 95% CI, 1.04-1.12; P = 1.29 × 10-4), but not large artery stroke, small vessel stroke, CAD and MI. In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD. CONCLUSIONS: This study found that genetic predisposition to PD is related to higher risk of IS and cardioembolic stroke in European population.
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Doença da Artéria Coronariana , AVC Embólico , Doença de Parkinson , Acidente Vascular Cerebral , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genéticaRESUMO
OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been proved to be a strong predictor of carotid atherosclerotic plaque, but the correlation between NLR and the stability of carotid plaque is not clear. Thus we conducted a study to evaluate the correlation between NLR and the stability of carotid atherosclerotic plaque, and to develop a new evaluation scale for rapid clinical evaluation of carotid plaque stability. METHODS: We recruited 528 patients with acute anterior circulation ischemic stroke who were in accordance with extracranial and intracranial large artery atherosclerosis of Chinese ischemic stroke subtype. Blood routine examination and carotid ultrasound examination were performed on admission. According to the ultrasonic characteristics, the patients were divided into plaque stabilization group and plaque instability group. RESULTS: There was significant difference in NLR between plaque stability and instability groups (P < 0.001). The risk of plaque instability increased with the increase of NLR (odds ratio (OR), 4.737; 95% confidence interval (CI), 3.404-6.592; P < 0.001). Receiver operating characteristic (ROC) curve showed that the critical point of NLR is 2.55 and the area under the curve (AUC) was 0.782 (95%CI, 0.740-0.823; P < 0.001). The best cut-off value of the evaluation scale was ≥ 4 points (sensitivity, 0.77; specificity, 0.75; accuracy, 0.76). CONCLUSION: There is a correlation between NLR and carotid plaque instability. NLR may be useful as a potential inflammation biomarker indicating the risk of unstable carotid plaques. The new scoring scale is a reliable index to predict the stability of carotid plaque.
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Estenose das Carótidas , AVC Isquêmico , Linfócitos , Neutrófilos , Placa Aterosclerótica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estenose das Carótidas/sangue , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/imunologia , Estenose das Carótidas/patologia , Feminino , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/imunologia , AVC Isquêmico/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: Daytime sleepiness is known to be related to stroke, but whether daytime sleepiness is a risk factor for stroke remains unclear. We conducted a two-sample Mendelian randomization study to assess the relationship between daytime sleepiness and stroke, ischemic stroke (IS) and IS subtypes. METHODS: Thirty-six single-nucleotide polymorphisms (SNPs) associated with daytime sleepiness were selected as instrumental variables, which were identified from a recent genome-wide association study(N = 452,071). Summary statistics of the SNPs on stroke, IS and IS subtypes were derived from the MEGASTROKE consortium with 40,585 stroke cases and 406,111 controls. RESULTS: We found that daytime sleepiness was associated with large artery stroke (OR, 6.75; 95%CI, 1.49-30.57; p = 0.013), but not with all stroke (OR, 1.29; 95%CI, 0.81-2.05; p = 0.282), all ischemic stroke(OR, 1.46; 95%CI, 0.90-2.39; p = 0.136), cardioembolic stroke(OR, 1.0; 95%CI, 0.39-2.64; p = 0.984), or small artery stroke(OR, 1.52; 95%CI, 0.46-5.05; p = 0.485). CONCLUSION: Our findings indicated that daytime sleepiness is causally associated with an increased risk of large artery stroke. Further studies are necessary to verify our results and explain the physiological mechanisms.
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Distúrbios do Sono por Sonolência Excessiva/complicações , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/etiologia , Estudos de Casos e Controles , Distúrbios do Sono por Sonolência Excessiva/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Fatores de Risco , Acidente Vascular Cerebral/genéticaRESUMO
OBJECTIVE: Observational studies have suggested that increased levels of education and cognition are associated with a reduced risk of epilepsy. However, such associations are easily influenced by confounding or reverse causality. Hence, we conducted a two-sample univariable and multivariable Mendelian randomization (MR) to estimate the total and independent causal effects of educational attainment and cognition on epilepsy risk. METHODS: We performed MR estimates on International League Against Epilepsy (ILAE) Consortium genome-wide association study (GWAS) data (15 212 epilepsy cases and 29 677 controls). We then validated the results in FinnGen (3424 epilepsy cases and 110 963 controls) and applied meta-analysis to all the results. RESULTS: In the meta-analysis of the ILAE and FinnGen results, genetically determined increased educational attainment was associated with a reduced risk of epilepsy (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.80-0.88; P < .001). Similarly, genetically determined increased cognitive function was associated with a reduced risk of epilepsy (OR 0.94, 95% CI 0.88-1.00, P = .043). When educational attainment and cognitive function were included in the same multivariable MR, only educational attainment was still associated with a reduced risk of epilepsy (OR 0.88, 95% CI 0.81-0.95, P = .002). SIGNIFICANCE: This MR study provides evidence to support that increased educational attainment can reduce the risk of developing epilepsy independent of cognitive function.
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Cognição , Escolaridade , Epilepsia/prevenção & controle , Epilepsia/psicologia , Causalidade , Estudos de Coortes , Epilepsia/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único , Medição de Risco , População BrancaRESUMO
We report on inapparent infections in adult/commercial tilapia in major tilapia fish farms in Guangdong. A total of 146 suspected isolates were confirmed to be S. agalactiae using an API 20 Strep system and specific PCR amplification. All isolates were identified as serotype Ia using multiplex serotyping PCR. An MLST assay showed single alleles of adhP (10), atr (2), glcK (2), glnA (1), pheS (1), sdhA (3) and tkt (2), and this profile was designated 'unique ST 7'. The analysis of virulence genes resulted in 10 clusters, of which dltr-bca-sodA-spb1-cfb-bac (62, 42.47%) was the predominant virulence gene profile. The PFGE analysis of S. agalactiae yielded 6 distinct PFGE types (A, B, C, D, F and G), of which Pattern C (103) was the predominant type, accounting for approximately 70.55% (103/146) of the total S. agalactiae strains. Therefore, unlike what has been found in juvenile tilapia, in which PFGE pattern D/F is the major prevalent pattern, we found that pattern C was the major prevalent pattern in inapparent infected adult/commercial tilapia in Guangdong, China. In conclusion, we close a gap in the current understanding of S. agalactiae epidemiology and propose that researchers should be alert for inapparent S. agalactiae infections in adult/commercial tilapia to prevent a potential threat to food safety.