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      Polymorphism in GRHL2 gene may contribute to noise-induced hearing loss susceptibility: a meta-analysis Translated title: Polimorfismo no gene GRHL2 pode contribuir para a suscetibilidade à perda auditiva induzida por ruído: uma metanálise

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Instruction

          Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting.

          Objective

          The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss.

          Methods

          A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association.

          Results

          Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594–0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062–1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514–0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054–1.379).

          Conclusion

          Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

          Resumo

          Introdução

          Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes.

          Objetivo

          Identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído.

          Método

          Uma pesquisa abrangente foi feita para coletar dados até 8 de julho de 2018. No fim, quatro artigos elegíveis foram incluídos nesta metanálise, abrangeram 2.410 indivíduos. As odds ratios agrupadas com intervalos de confiança de 95% foram usadas para avaliar a força da associação.

          Resultados

          Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379).

          Conclusão

          O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.

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          Most cited references39

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          Bias in meta-analysis detected by a simple, graphical test.

          Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
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              Genome-wide strategies for detecting multiple loci that influence complex diseases.

              After nearly 10 years of intense academic and commercial research effort, large genome-wide association studies for common complex diseases are now imminent. Although these conditions involve a complex relationship between genotype and phenotype, including interactions between unlinked loci, the prevailing strategies for analysis of such studies focus on the locus-by-locus paradigm. Here we consider analytical methods that explicitly look for statistical interactions between loci. We show first that they are computationally feasible, even for studies of hundreds of thousands of loci, and second that even with a conservative correction for multiple testing, they can be more powerful than traditional analyses under a range of models for interlocus interactions. We also show that plausible variations across populations in allele frequencies among interacting loci can markedly affect the power to detect their marginal effects, which may account in part for the well-known difficulties in replicating association results. These results suggest that searching for interactions among genetic loci can be fruitfully incorporated into analysis strategies for genome-wide association studies.
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                Author and article information

                Contributors
                Journal
                Braz J Otorhinolaryngol
                Braz J Otorhinolaryngol
                Brazilian Journal of Otorhinolaryngology
                Elsevier
                1808-8694
                1808-8686
                23 February 2019
                May-Jun 2020
                23 February 2019
                : 86
                : 3
                : 370-375
                Affiliations
                [a ]Nanjing Municipal Center for Disease Control and Prevention, Department of HIV/AIDS/STI Prevention and Control, Jiangsu, China
                [b ]Southeast University, School of Public Health, Department of Epidemiology and Health Statistics, Key Laboratory of Environmental Medicine Engineering, Jiangsu, China
                [c ]Nanjing Municipal Center for Disease Control and Prevention, Environmental Health Division, Jiangsu, China
                [d ]Nanjing Zhongyangmen Community Health Service Center, Kang’ai Hospital, Center of Diagnosis and Treatment for Developmental Dysplasia of the Hip, Jiangsu, China
                Author notes
                [* ]Corresponding author. charliehao@ 123456msn.com
                Article
                S1808-8694(18)30439-7
                10.1016/j.bjorl.2019.01.003
                9422585
                30853467
                8030808d-7cd5-445e-b8d7-06d69ef0b6ff
                © 2019 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 9 July 2018
                : 2 January 2019
                Categories
                Original Article

                noise-induced hearing loss,grainyhead like 2,molecular epidemiology,polymorphism,meta-analysis,perda auditiva induzida por ruído,epidemiologia molecular,polimorfismo,metanálise

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