scholarly journals The association between genetic polymorphisms in ABCG2 and SLC2A9 and urate: an updated systematic review and meta-analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Thitiya Lukkunaprasit ◽  
Sasivimol Rattanasiri ◽  
Saowalak Turongkaravee ◽  
Naravut Suvannang ◽  
Atiporn Ingsathit ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Serum Urate ◽  
High Serum ◽  
Minor Allele ◽  
Risk Scores ◽  
Mixed Effect ◽  
Lower Odds ◽  
Replication Studies ◽  
Minor Alleles ◽  
Patients At Risk

Abstract Background Replication studies showed conflicting effects of ABCG2 and SLC2A9 polymorphisms on gout and serum urate. This meta-analysis therefore aimed to pool their effects across studies. Methods Studies were located from MEDLINE and Scopus from inception to 17th June 2018. Observational studies in adults with any polymorphism in ABCG2 or SLC2A9, and outcome including gout, hyperuricemia, and serum urate were included for pooling. Data extractions were performed by two independent reviewers. Genotype effects were pooled stratified by ethnicity using a mixed-effect logistic model and a multivariate meta-analysis for dichotomous and continuous outcomes. Results Fifty-two studies were included in the analysis. For ABCG2 polymorphisms, mainly studied in Asians, carrying 1–2 minor-allele-genotypes of rs2231142 and rs72552713 were respectively about 2.1–4.5 and 2.5–3.9 times higher odds of gout than non-minor-allele-genotypes. The two rs2231142-risk-genotypes also had higher serum urate about 11–18 μmol/l. Conversely, carrying 1–2 minor alleles of rs2231137 was about 36–57% significantly lower odds of gout. For SLC2A9 polymorphisms, mainly studied in Caucasians, carrying 1–2 minor alleles of rs1014290, rs6449213, rs6855911, and rs7442295 were about 25–43%, 31–62%, 33–64%, and 35–65% significantly lower odds of gout than non-minor-allele-genotypes. In addition, 1–2 minor-allele-genotypes of the latter three polymorphisms had significantly lower serum urate about 20–49, 21–51, and 18–54 μmol/l than non-minor-allele-genotypes. Conclusions Our findings should be useful in identifying patients at risk for gout and high serum urate and these polymorphisms may be useful in personalized risk scores. Trial registration PROSPERO registration number: CRD42018105275.

scholarly journals 300Association between rs2231142 of ABCG2 and gout, hyperuricemia and uric acid: Systematic review and meta-analysis

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Thitiya Lukkunaprasit ◽  
Sasivimol Rattanasiri ◽  
Saowalak Turongkaravee ◽  
Atiporn Ingsathit ◽  
John Attia ◽  
...  
Keyword(s):  
Uric Acid ◽  
Association Studies ◽  
Meta Analysis ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Mixed Effect ◽  
Gene Effects ◽  
Replication Studies ◽  
Hardy Weinberg Equilibrium ◽  
Mean Differences

Abstract Background Genome-wide association studies showed that rs2231142 (C421A) of ABCG2 gene has strong effects on gout and uric acid (UA). However, replication studies showed conflicting results. We aimed to pool effects of rs2231142 on gout, hyperuricemia, and UA across studies. Methods Studies were located from MEDLINE and Scopus until 17th June 2018. Data extractions were performed by two independent reviewers. Hardy-Weinberg equilibrium was checked. Genotype effects were pooled by ethnicity using mixed-effect logistic model for gout and hyperuricemia and multivariate meta-analysis for UA. Publication bias was assessed using funnel plots and Egger’s tests. Results Thirty studies were eligible; 21, 5, and 8 studies assessed association between rs2231142 and gout, hyperuricemia, and UA, respectively. Carrying AA and CA genotypes were 3.2 (2.4, 4.4) and 1.6 (1.5, 1.8) higher odds to develop gout in Caucasians. Likewise, in Asians, the ORs for corresponding genotypes were 4.5 (4.1, 5.0) and 2.1 (2.0, 2.3) for gout; 2.3 (1.8, 2.8) and 1.6 (1.4, 1.8) for hyperuricemia. Mean differences of UA in Caucasians carrying AA and CA were 50.4 (32.7, 68.2) and 19.5 (14.2, 24.7) µmol/l compared with those carrying CC genotype while in Asians, they were 18.4 (8.7, 28.1) and 11.5 (4.1, 18.9) µmol/l, respectively. Additive gene effects were suggested. Conclusions Significant effects of rs2231142 on gout, hyperuricemia, and elevated UA were confirmed. Our findings should be useful in personalized risk scores for prediction of gout and diseases related to high UA. Key messages rs2231142 increased the risk of gout and UA in Asians and Caucasians

scholarly journals GENOME-WIDE META-ANALYSIS SUPPORTS HETEROGENEITY IN POLYGENIC ARCHITECTURE OF DISABILITY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S87-S87
Author(s):  
Alexander Kulminski ◽  
Chansuk Kang ◽  
Yury Loika ◽  
Eric Stallard ◽  
Irina Culminskaya
Keyword(s):  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Well Being ◽  
Risk Scores ◽  
Genome Wide ◽  
Nominal Significance ◽  
Individual Snps ◽  
Replication Strategy ◽  
Minor Alleles ◽  
Using Data

Abstract Disability and frailty increase steeply with age after midlife. They comprise broad, non-specific aging-related health/well-being declines. Understanding the molecular mechanisms of these declines could help in combating processes related to intrinsic aging. We performed genome-wide meta-analysis of disability using data on N=12,550 disabled individuals of Caucasian ancestry from five independent studies with N=24,068 genotyped participants. Disability was measured using the Activities of Daily Living (ADL) scale. A subject was considered disabled if he/she had at least one ADL impairment. All subjects in our study were aged 50+ years. The analysis followed a discovery-replication strategy using two studies as discovery samples and three others as replication samples. At the discovery stage, we selected SNPs at nominal significance (p<0.05) and evaluated their associations with disability in the replication samples. Meta-analysis across all studies identified 30 SNPs (24 loci) at p<10e-4. SNPs from four loci (chromosomes 2, 8, and 12) attained suggestive significances at p<10-5. We constructed two polygenic risk scores (PGRS) using these 30 SNPs whose minor alleles were positively (19 SNPs) and negatively (11 SNPs) associated with disability, PGRS_p and PGRS_n, respectively. Meta-analysis across all studies identified strong effects for PGRS_p (beta=0.436, p=1.18×10e-32) and PGRS_n (beta=-0.426, p=8.74×10e-19). The associations for the PGRSs observed in two discovery studies were replicated in three independent studies. The lack of genome-wide significant effects of individual SNPs combined with the highly significant effects of the PGRSs shows that, in line with the heterogeneous origin of disability, its genetic architecture is of highly heterogeneous polygenic origin.

scholarly journals Serum Urate and the Risk of Parkinson's Disease: Results From a Meta-Analysis

2013 ◽  
Vol 40 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Chunhong Shen ◽  
Yi Guo ◽  
Wei Luo ◽  
Chen Lin ◽  
Meiping Ding
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Web Of Science ◽  
Meta Analysis ◽  
Serum Urate ◽  
High Serum ◽  
Protective Effects ◽  
Inclusion Criteria ◽  
Serum Urate Level

Objective:Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD.Methods:We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender.Results:Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72).Conclusions:In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.

Identification of and Correction for Publication Bias: Comment

2019 ◽  
Author(s):  
Amanda Kvarven ◽  
Eirik Strømland ◽  
Magnus Johannesson
Keyword(s):  
Publication Bias ◽  
False Positive ◽  
Large Scale ◽  
Meta Analysis ◽  
False Positive Rate ◽  
Effect Sizes ◽  
Replication Studies ◽  
Moderate Reduction ◽  
Positive Rate ◽  
Meta Analyses

Andrews & Kasy (2019) propose an approach for adjusting effect sizes in meta-analysis for publication bias. We use the Andrews-Kasy estimator to adjust the result of 15 meta-analyses and compare the adjusted results to 15 large-scale multiple labs replication studies estimating the same effects. The pre-registered replications provide precisely estimated effect sizes, which do not suffer from publication bias. The Andrews-Kasy approach leads to a moderate reduction of the inflated effect sizes in the meta-analyses. However, the approach still overestimates effect sizes by a factor of about two or more and has an estimated false positive rate of between 57% and 100%.

scholarly journals TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: A meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients

2012 ◽  
Vol 33 (3) ◽  
pp. 507-514 ◽  
Author(s):  
Fabrizio D'Ascenzo ◽  
Giuseppe Biondi-Zoccai ◽  
Claudio Moretti ◽  
Mario Bollati ◽  
Pierluigi Omedè ◽  
...  
Keyword(s):  
Validation Studies ◽  
Acute Coronary Syndromes ◽  
Meta Analysis ◽  
Risk Scores ◽  
Coronary Syndromes

scholarly journals A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Michelle Elaine Orme ◽  
Carmen Andalucia ◽  
Sigrid Sjölander ◽  
Xavier Bossuyt
Keyword(s):  
Connective Tissue ◽  
Indirect Immunofluorescence ◽  
Meta Analysis ◽  
Connective Tissue Diseases ◽  
Test Accuracy ◽  
Initial Screening ◽  
Case Control Studies ◽  
Cross Sectional ◽  
Mixed Effect ◽  
Mixed Effect Models

AbstractObjectivesTo compare indirect immunofluorescence (IIF) for antinuclear antibodies (ANA) against immunoassays (IAs) as an initial screening test for connective tissue diseases (CTDs).MethodsA systematic literature review identified cross-sectional or case-control studies reporting test accuracy data for IIF and enzyme-linked immunosorbent assays (ELISA), fluorescence enzyme immunoassay (FEIA), chemiluminescent immunoassay (CLIA) or multiplex immunoassay (MIA). The meta-analysis used hierarchical, bivariate, mixed-effect models with random-effects by test.ResultsDirect comparisons of IIF with ELISA showed that both tests had good sensitivity (five studies, 2321 patients: ELISA: 90.3% [95% confidence interval (CI): 80.5%, 95.5%] vs. IIF at a cut-off of 1:80: 86.8% [95% CI: 81.8%, 90.6%]; p = 0.4) but low specificity, with considerable variance across assays (ELISA: 56.9% [95% CI: 40.9%, 71.5%] vs. IIF 1:80: 68.0% [95% CI: 39.5%, 87.4%]; p = 0.5). FEIA sensitivity was lower than IIF sensitivity (1:80: p = 0.005; 1:160: p = 0.051); however, FEIA specificity was higher (seven studies, n = 12,311, FEIA 93.6% [95% CI: 89.9%, 96.0%] vs. IIF 1:80 72.4% [95% CI: 62.2%, 80.7%]; p < 0.001; seven studies, n = 3251, FEIA 93.5% [95% CI: 91.1%, 95.3%] vs. IIF 1:160 81.1% [95% CI: 73.4%, 86.9%]; p < 0.0001). CLIA sensitivity was similar to IIF (1:80) with higher specificity (four studies, n = 1981: sensitivity 85.9% [95% CI: 64.7%, 95.3%]; p = 0.86; specificity 86.1% [95% CI: 78.3%, 91.4%]). More data are needed to make firm inferences for CLIA vs. IIF given the wide prediction region. There were too few studies for the meta-analysis of MIA vs. IIF (MIA sensitivity range 73.7%–86%; specificity 53%–91%).ConclusionsFEIA and CLIA have good specificity compared to IIF. A positive FEIA or CLIA test is useful to support the diagnosis of a CTD. A negative IIF test is useful to exclude a CTD.

Do sexist jokes increase rape proclivity among males high in hostile sexism? Evidence from two pre-registered direct replications of Thomae & Viki (2013)

2021 ◽  
Author(s):  
Neil McLatchie ◽  
Manuela Thomae
Keyword(s):  
Bayes Factor ◽  
Alternative Hypothesis ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Original Study ◽  
Bayes Factors ◽  
Hostile Sexism ◽  
Replication Studies ◽  
Open Research ◽  
Rape Proclivity

Thomae and Viki (2013) reported that increased exposure to sexist humour can increase rape proclivity among males, specifically those who score high on measures of Hostile Sexism. Here we report two pre-registered direct replications (N = 530) of Study 2 from Thomae and Viki (2013) and assess replicability via (i) statistical significance, (ii) Bayes factors, (iii) the small-telescope approach, and (iv) an internal meta-analysis across the original and replication studies. The original results were not supported by any of the approaches. Combining the original study and the replications yielded moderate evidence in support of the null over the alternative hypothesis with a Bayes factor of B = 0.13. In light of the combined evidence, we encourage researchers to exercise caution before claiming that brief exposure to sexist humour increases male’s proclivity towards rape, until further pre-registered and open research demonstrates the effect is reliably reproducible.

Complications of transradial versus transfemoral access for neuroendovascular procedures: a meta-analysis

2021 ◽  
pp. neurintsurg-2021-018032
Author(s):  
Derrek Schartz ◽  
Sajal Medha K Akkipeddi ◽  
Nathaniel Ellens ◽  
Redi Rahmani ◽  
Gurkirat Singh Kohli ◽  
...  
Keyword(s):  
Literature Review ◽  
Meta Analysis ◽  
Final Analysis ◽  
Case Control ◽  
Random Effects Model ◽  
Inclusion Criteria ◽  
Access Site ◽  
Lower Odds ◽  
Significant Difference ◽  
Study Heterogeneity

BackgroundTransradial access (TRA) has gained increased usage among neurointerventionalists. However, the overall safety profile of access site complications (ASCs) and non-access site complications (NASCs) of TRA versus transfemoral access (TFA) for neuroendovascular procedures remains unclear.MethodsA systematic literature review and meta-analysis using a random effects model was conducted to investigate the pooled odds ratios (OR) of ASCs and NASCs. Randomized, case–control, and cohort studies comparing access-related complications were analyzed. An assessment of study heterogeneity and publication bias was also completed.ResultsSeventeen comparative studies met the inclusion criteria for final analysis. Overall, there was a composite ASC rate of 1.8% (49/2767) versus 3.2% (168/5222) for TRA and TFA, respectively (P<0.001). TRA was associated with a lower odds of ASC compared with TFA (OR 0.42; 95% CI 0.25 to 0.68, P<0.001, I2=31%). There was significantly lower odds of complications within the intervention and diagnostic subgroups. For NASC, TRA had a lower composite incidence of complications than TFA at 1.2% (31/2586) versus 4.2% (207/4909), P<0.001). However, on meta-analysis, we found no significant difference overall between TRA and TFA for NASCs (OR 0.79; 95% CI 0.51 to 1.22, P=0.28, I2=0%), which was also the case on subgroup analysis.ConclusionOn meta-analysis, the current literature indicates that TRA is associated with a lower incidence of ASCs compared with TFA, but is not associated with a lower rate of NASCs.

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