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Pathway analysis of rare variants for the clustered phenotypes by using hierarchical structured components analysis.

Abstract：

BACKGROUNDS:Recent large-scale genetic studies often involve clustered phenotypes such as repeated measurements. Compared to a series of univariate analyses of single phenotypes, an analysis of clustered phenotypes can be useful for substantially increasing statistical power to detect more genetic associations. Moreover, for the analysis of rare variants, incorporation of biological information can boost weak effects of the rare variants. RESULTS:Through simulation studies, we showed that the proposed method outperforms other method currently available for pathway-level analysis of clustered phenotypes. Moreover, a real data analysis using a large-scale whole exome sequencing dataset of 995 samples with metabolic syndrome-related phenotypes successfully identified the glyoxylate and dicarboxylate metabolism pathway that could not be identified by the univariate analyses of single phenotypes and other existing method. CONCLUSION:In this paper, we introduced a novel pathway-level association test by combining hierarchical structured components analysis and penalized generalized estimating equations. The proposed method analyzes all pathways in a single unified model while considering their correlations. C/C++ implementation of PHARAOH-GEE is publicly available at http://statgen.snu.ac.kr/software/pharaoh-gee/ .

journal_name

BMC Med Genomics

journal_title

BMC medical genomics

authors

Lee S,Kim S,Kim Y,Oh B,Hwang H,Park T

doi

10.1186/s12920-019-0517-4

subject

Has Abstract

pub_date

2019-07-11 00:00:00

pages

100

issue

Suppl 5

issn

1755-8794

pii

10.1186/s12920-019-0517-4

journal_volume

12

pub_type

杂志文章

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