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A modified generalized Fisher method for combining probabilities from dependent tests.

ABSTRACT: Rapid developments in molecular technology have yielded a large amount of high throughput genetic data to understand the mechanism for complex traits. The increase of genetic variants requires hundreds and thousands of statistical tests to be performed simultaneously in analysis, which poses a challenge to control the overall Type I error rate. Combining p-values from multiple hypothesis testing has shown promise for aggregating effects in high-dimensional genetic data analysis. Several p-value combining methods have been developed and applied to genetic data; see Dai et al. (2012b) for a comprehensive review. However, there is a lack of investigations conducted for dependent genetic data, especially for weighted p-value combining methods. Single nucleotide polymorphisms (SNPs) are often correlated due to linkage disequilibrium (LD). Other genetic data, including variants from next generation sequencing, gene expression levels measured by microarray, protein and DNA methylation data, etc. also contain complex correlation structures. Ignoring correlation structures among genetic variants may lead to severe inflation of Type I error rates for omnibus testing of p-values. In this work, we propose modifications to the Lancaster procedure by taking the correlation structure among p-values into account. The weight function in the Lancaster procedure allows meaningful biological information to be incorporated into the statistical analysis, which can increase the power of the statistical testing and/or remove the bias in the process. Extensive empirical assessments demonstrate that the modified Lancaster procedure largely reduces the Type I error rates due to correlation among p-values, and retains considerable power to detect signals among p-values. We applied our method to reassess published renal transplant data, and identified a novel association between B cell pathways and allograft tolerance.

SUBMITTER: Dai H

PROVIDER: S-EPMC3929847 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A modified generalized Fisher method for combining probabilities from dependent tests.

Dai Hongying H Leeder J Steven JS Cui Yuehua Y

Frontiers in genetics 20140220

Rapid developments in molecular technology have yielded a large amount of high throughput genetic data to understand the mechanism for complex traits. The increase of genetic variants requires hundreds and thousands of statistical tests to be performed simultaneously in analysis, which poses a challenge to control the overall Type I error rate. Combining p-values from multiple hypothesis testing has shown promise for aggregating effects in high-dimensional genetic data analysis. Several p-value ...[more]

PMID: 24600471

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Project description:Harnessing the traditional ecological knowledge (TEK) of local communities has the potential to enhance conservation planning in developing regions. Marine protected areas (MPAs) that incorporate traditional beliefs about reef tenure are generally more successful in reaching conservation goals and ensuring the participation of local fishermen on vulnerable tropical reef systems. Fiji possesses a unique system of traditional reef management in which local clans or villages, called mataqali, control individual units of a reef, known as qoliqoli, and make independent management decisions based on traditional beliefs and conservation concerns. This is an example of a system, known as customary marine tenure, which has attracted interest from conservation scientists hoping to set up MPAs in vulnerable regions. As one example of this grassroots participation, Nagigi village on the Fijian island of Vanua Levu has expressed interest in setting up an MPA in part of its qoliqoli because of concerns about overfishing. In response to this interest, we took a two-pronged approach to assessing Nagigi's fishery status and conservation needs, first conducting a fishery-independent species survey using destructive sampling and then focusing on fisheries targets identified through fisher interviews. These interviews allowed us to identify heavily targeted species, assess villagers' understanding of reef dynamics over 30 or 40 years of fisheries expansion, and evaluate village support and expectations for a proposed conservation program. Based on our findings we recommend a temporary closure to be in effect for at least three years, allowing one of the more important fishery targets, Lethrinus harak (Forsskål, 1775; Lethrinidae), to complete at least one generation within the reserve. The methodology of matching the proposed marine protected area with the life histories and ecologies of heavily targeted species identified through fisherman and -woman interviews can offer a template for future conservation projects that seek to synthesize indigenous peoples' needs and knowledge with ecological data.

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A modified generalized Fisher method for combining probabilities from dependent tests.

Publications

A modified generalized Fisher method for combining probabilities from dependent tests.

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