Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases.
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SUBMITTER: Math N
PROVIDER: S-EPMC6848040 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases.
Math Nikhil N Han Thang S TS Lubomirova Irina I Hill Robert R Bentley Paul P Sharma Pankaj P
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 20190729 12
<h4>Background</h4>The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants.<h4>Methods</h4>PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by val ...[more]
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Project description:Refractive error is a complex ocular trait governed by both genetic and environmental factors and possibly their interplay. Thus far, data on the interaction between genetic variants and environmental risk factors for refractive errors are largely lacking. By using findings from recent genome-wide association studies, we investigated whether the main environmental factor, education, modifies the effect of 40 single nucleotide polymorphisms on refractive error among 8461 adults from five studies including ethnic Chinese, Malay and Indian residents of Singapore. Three genetic loci SHISA6-DNAH9, GJD2 and ZMAT4-SFRP1 exhibited a strong association with myopic refractive error in individuals with higher secondary or university education (SHISA6-DNAH9: rs2969180 A allele, ? = -0.33 D, P = 3.6 × 10(-6); GJD2: rs524952 A allele, ? = -0.31 D, P = 1.68 × 10(-5); ZMAT4-SFRP1: rs2137277 A allele, ? = -0.47 D, P = 1.68 × 10(-4)), whereas the association at these loci was non-significant or of borderline significance in those with lower secondary education or below (P for interaction: 3.82 × 10(-3)-4.78 × 10(-4)). The evidence for interaction was strengthened when combining the genetic effects of these three loci (P for interaction = 4.40 × 10(-8)), and significant interactions with education were also observed for axial length and myopia. Our study shows that low level of education may attenuate the effect of risk alleles on myopia. These findings further underline the role of gene-environment interactions in the pathophysiology of myopia.
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Project description:BackgroundPrevious studies indicate that low initial sensitivity to alcohol may be a risk factor for later alcohol misuse. Evidence suggests that initial sensitivity is influenced by genetic factors, but few molecular genetic studies have been reported.MethodsWe conducted a meta-analysis of 2 population-based genome-wide association studies of the Self-Rating of the Effects of Alcohol scale. Our final sample consisted of 7,339 individuals (82.3% of European descent; 59.2% female) who reported having used alcohol at least 5 times. In addition, we estimated single nucleotide polymorphism (SNP)-based heritability and conducted a series of secondary aggregate genetic analyses.ResultsNo individual locus reached genome-wide significance. Gene and set based analyses, both overall and using tissue-specific expression data, yielded largely null results, and genes previously implicated in alcohol problems and consumption were overall not associated with initial sensitivity. Only 1 gene set, related to hormone signaling and including core clock genes, survived correction for multiple testing. A meta-analysis of SNP-based heritability resulted in a modest estimate of hSNP2 = 0.19 (SE = 0.10), though this was driven by 1 sample (N = 3,683, hSNP2 = 0.36, SE = 0.14, p = 0.04). No significant genetic correlations with other relevant outcomes were observed.ConclusionsFindings yielded only modest support for a genetic component underlying initial alcohol sensitivity. Results suggest that its biological underpinnings may diverge somewhat from that of other alcohol outcomes and may be related to core clock genes or other aspects of hormone signaling. Larger samples, ideally of prospectively assessed samples, are likely necessary to improve gene identification efforts and confirm the current findings.
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Project description:Disentangling the genetic and environmental influences of gambling is important for explaining the roots of individual differences in gambling behavior and providing guidance for precaution and intervention, but we are unaware of any comprehensive and systematic quantitative meta-analysis. We systematically identified 18 twin studies on gambling in the meta-analysis. The correlation coefficients within monozygotic (MZ) and dizygotic (DZ) twins, along with the corresponding sample size, were used to calculate the proportion of the total variance accounted for by additive genes (A), dominant genes (D), the shared environment (C), and the non-shared environment plus measurement error (E). We further assessed the moderating effects of gambling assessment (symptom oriented assessment vs. behavior oriented assessment), age, and sex. The whole sample analyses showed moderate additive genetic (a2 = 0.50) and non-shared environmental influences (e2 = 0.50) on gambling. The magnitude of the genetic influence (a2) was higher for disordered gambling assessed with symptom oriented assessment (53%) than for general gambling assessed with behavior oriented assessment (41%). Additionally, the magnitude of the genetic influence (a2) was higher for adults (53%) than adolescents (42%). Genetic influence (a2) was greater for male (47%) gambling than female (28%) gambling. Shared environment had noticeable effects on female gambling (c2 = 14%) but zero effect on male gambling. In conclusion, gambling behavior was moderately heritable and moderately influenced by non-shared environmental factors. Gambling assessment, age, and sex significantly moderated the magnitude of genetic and environmental influences on gambling. Note that the number of studies might serve as a limitation.
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Project description:BackgroundRecent studies have reported that lncRNA (long noncoding RNAs) antisense non-coding RNA in the INK4 locus (ANRIL) plays important roles in the development of atherosclerosis through regulating cell apoptosis, proliferation, and adhesion. GWAS (genome-wide association studies) identified common genetic variants within ANRIL could confer risk of ischemic stroke (IS) in southern Sweden.MethodsWe performed a case-control study, including 567 IS patients and 552 healthy controls from unrelated northern Chinese Han population, aiming to explore the association between lncRNA ANRIL rs2383207, rs4977574 polymorphisms and the risk of IS. Subsequently we implemented a meta-analysis to further assess the relationship of these variants and the disease.ResultsIn our case-control study, no significant associations were observed in all models between above 2 polymorphisms and IS. Next in our subgroup analysis, we detected significant association between GA genotype of rs4977574 and the increased risk of LAA-IS (large-artery atherosclerotic ischemic stroke), similar elevated risk also appeared in the GG + GA genotype under the dominant model (P = .048, OR = 1.385, 95% CIs 1.002-1.914; P = .040, OR = 1.378, 95% CIs 1.015-1.872, respectively). As for rs2383207, negative results were obtained under all models and subgroups. Our meta-analysis showed a significant association between rs4977574 polymorphism and IS risk in allele model (G vs A P = .002, OR = 1.137, 95% CIs 1.048-1.234); with respect to rs2383207 polymorphism, no significant association between that and the risk of IS was detected under the dominant model (GA + AA vs GG, P = .061, OR = 0.923, 95% CIs 0.849-1.004), or recessive model (AA vs GA + GG, P = .656, OR = 0.972, 95% CIs 0.858-1.101), or allele model (A vs G, P = .326, OR = 0.952, 95% CIs 0.863-1.050). Likewise, no significant association between rs2383207 and IS was found in different stoke subtypes (P > .05).ConclusionsOur findings indicated G allele of lncRNA ANRIL rs4977574 could increase the risk of IS, and the variant may be associated with susceptibility to LAA-IS in Chinese Han population.
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Project description:BACKGROUND:Prognostic models have been increasingly developed to predict complete recovery in ischemic stroke. However, questions arise about the performance characteristics of these models. The aim of this study was to systematically review and synthesize performance of existing prognostic models for complete recovery in ischemic stroke. METHODS:We searched journal publications indexed in PUBMED, SCOPUS, CENTRAL, ISI Web of Science and OVID MEDLINE from inception until 4 December, 2017, for studies designed to develop and/or validate prognostic models for predicting complete recovery in ischemic stroke patients. Two reviewers independently examined titles and abstracts, and assessed whether each study met the pre-defined inclusion criteria and also independently extracted information about model development and performance. We evaluated validation of the models by medians of the area under the receiver operating characteristic curve (AUC) or c-statistic and calibration performance. We used a random-effects meta-analysis to pool AUC values. RESULTS:We included 10 studies with 23 models developed from elderly patients with a moderately severe ischemic stroke, mainly in three high income countries. Sample sizes for each study ranged from 75 to 4441. Logistic regression was the only analytical strategy used to develop the models. The number of various predictors varied from one to 11. Internal validation was performed in 12 models with a median AUC of 0.80 (95% CI 0.73 to 0.84). One model reported good calibration. Nine models reported external validation with a median AUC of 0.80 (95% CI 0.76 to 0.82). Four models showed good discrimination and calibration on external validation. The pooled AUC of the two validation models of the same developed model was 0.78 (95% CI 0.71 to 0.85). CONCLUSIONS:The performance of the 23 models found in the systematic review varied from fair to good in terms of internal and external validation. Further models should be developed with internal and external validation in low and middle income countries.
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Project description:BackgroundIn the past decade, accumulated evidence has suggested that genetic variation is related to the pathogenesis of osteosarcoma. Although there are a large number of studies on the association between genetic variation and osteosarcoma, their results are inconsistent. To clarify these findings, we performed a systematic meta-analysis using allelic contrasts for each gene-specific single nucleotide variants with all available data in the field of osteosarcoma.MethodsThe literature search for relevant studies was conducted in PubMed, Embase, and Cochrane databases. Pooled ORs and 95% CI values were calculated by the random-effects model using the Comprehensive Meta-analysis version 2.0 software package. Heterogeneity between studies was examined by the Cochran's Q-test.ResultsThe 32 genome-wide case-control population-based studies, involving 15,336 study subjects (6924 cases and 8412 controls), were included in this meta-analysis. We analyzed 24 single nucleotide variants (SNVs) in 14 genes. We identified 12 SNVs in CTLA-4, IL-8, MDM2, PRCKG, RECQL5, TNF-a, TP53, XRCC3, and VEGF that correlated with osteosarcoma susceptibility. The average pooled odds ratio for the 9 risk alleles was 2.082 (range: 1.585 to 3.262). These included CTLA-4 rs231775, CTLA-4 rs5742909, PRCKG rs454006, RECQL5 rs820196, TNF-α rs1800629, TP53 rs1042522, XRCC3 rs861539, VEGF rs699947, and VEGF rs3025039. The average pooled odds ratio for the 3 protective alleles, IL-8 rs4073, MDM2 rs1690916, and VEGF rs2010963, was 0.606 (range: 0.510-0.719). Publication bias was not observed among the studies reporting positively correlated SNVs. The pooled odds ratios for the SNVs that correlated with osteosarcoma risk showed homogeneity.ConclusionOur results provide powerful information for tracking the most viable gene candidates. Further studies with larger multiethnicity populations and investigations of the potential biological roles of these genetic variants in osteosarcoma should be conducted.
| S-EPMC6160068 | biostudies-literature
Project description:Stroke, either ischemic or hemorrhagic, is the leading cause of death and morbidity worldwide. Identifying the risk factors is a prerequisite step for stroke prevention and treatment. It is believed that a major portion of the currently unidentified risk factors is of genetic origin. Consistent with this idea, numerous potential risk alleles for stroke have been reported, however, the genetic evidence so far is not conclusive. The major goal of this review is to update the current knowledge about the genetic predisposition to the common multifactorial stroke, and to provide a bird's-eye view of this fast moving field. We selectively review and meta-analyze the related English literatures in public domain (PubMed) from 2000 onward, including the original reports and meta-analyses, to evaluate the genetic risk factors of common multifactorial stroke. The results indicated that we reviewed and meta-analyzed original reports and existing meta-analyses that studied the genetic predisposition to the common multifactorial stroke. Some original reports and meta-analyses were specific for ischemic stroke and others were for hemorrhagic stroke only. We also evaluated the major evolving issues in this field and discussed the future directions. In conclusion, strong evidences suggest that genetic risk factors contribute to common multifactorial stroke, and many genetic risk genes have been implicated in the literatures. However, not a single risk allele has been conclusively approved.
| S-EPMC4358587 | biostudies-literature
Project description:Background: Several studies investigated the relationship between antisense non-coding RNA in the INK4 locus (ANRIL) variants and the risk of ischemic stroke (IS), yet whether ANRIL variants are associated with IS remain controversial. Therefore, we performed the present study to obtain a more conclusive result. Methods: Literature retrieval was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs2383206 (recessive model: P=0.002, OR = 1.22, 95%CI 1.08-1.38; allele model: P=0.003, OR = 0.90, 95%CI 0.84-0.96) and rs10757274 (allele model: P=0.006, OR = 0.91, 95%CI 0.86-0.97) variants were significantly associated with an increased risk of IS. Further subgroup analyses by ethnicity revealed that rs2383206, rs10757274 and rs10757278 variants were all significantly correlated with an increased risk of IS in Asians. Additionally, rs10757278 polymorphism was also significantly correlated with an increased risk of IS in Caucasians. Conclusions: Our findings indicated that rs2383206, rs10757274 and rs10757278 variants may impact individual susceptibility to IS in Asians. Moreover, rs10757278 polymorphism may also impact individual susceptibility to IS in Caucasians.
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