JEPEGMIX2: improved gene-level joint analysis of eQTLs in cosmopolitan cohorts

被引：6

作者：

Chatzinakos, Chris ^{[1
]}

Lee, Donghyung ^{[2
]}

Webb, Bradley T. ^{[1
]}

Vladimirov, Vladimir I. ^{[1
]}

Kendler, Kenneth S. ^{[1
]}

Bacanu, Silviu-Alin ^{[1
]}

机构：

[1] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA

[2] Jackson Lab Genom Med, Farmington, CT 06032 USA

来源：

BIOINFORMATICS | 2018年 / 34卷 / 02期

关键词：

GENOME-WIDE ASSOCIATION; HERITABILITY; EXPRESSION; DISEASES; SNPS;

D O I：

10.1093/bioinformatics/btx509

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Motivation: To increase detection power, researchers use gene level analysis methods to aggregate weak marker signals. Due to gene expression controlling biological processes, researchers proposed aggregating signals for expression Quantitative Trait Loci (eQTL). Most gene-level eQTL methods make statistical inferences based on (i) summary statistics from genome-wide association studies (GWAS) and (ii) linkage disequilibrium patterns from a relevant reference panel. While most such tools assume homogeneous cohorts, our Gene-level Joint Analysis of functional SNPs in Cosmopolitan Cohorts (JEPEGMIX) method accommodates cosmopolitan cohorts by using heterogeneous panels. However, JEPGMIX relies on brain eQTLs from older gene expression studies and does not adjust for background enrichment in GWAS signals. Results: We propose JEPEGMIX2, an extension of JEPEGMIX. When compared to JPEGMIX, it uses (i) cis-eQTL SNPs from the latest expression studies and (ii) brains specific (sub) tissues and tissues other than brain. JEPEGMIX2 also (i) avoids accumulating averagely enriched polygenic information by adjusting for background enrichment and (ii) to avoid an increase in false positive rates for studies with numerous highly enriched (above the background) genes, it outputs gene q-values based on Holm adjustment of P-values.

引用

页码：286 / 288

页数：3

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