Pathway analysis for a genome-wide association study of pneumoconiosis.

Abstract:

OBJECTIVE:The aim of this investigation was to identify pathways involved in pneumoconiosis susceptibility, clarify their potential mechanisms, and generate SNP-to-gene to pathway hypotheses using an analytical pathway-based approach. METHODS:The identify candidate causal SNPs and pathways (ICSNPathway) was used to perform pathway analysis of a GWAS dataset for pneumoconiosis, which, after quality control filtering, harbored genotypes of 710,999 SNPs in 202 pneumoconiosis cases and 198 exposed controls. The first stage involved the pre-selection of candidate SNPs by linkage disequilibrium analysis and functional annotation of the most significant SNPs; the second stage involved annotation of biological mechanisms for the selected candidate SNPs using improved-gene set enrichment analysis. RESULTS:ICSNPathway analysis identified 18 candidate SNPs, involving 13 genes and 30 candidate pathways and revealed 13 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was that rs8120 and rs2292151 alters the role of TICAM1, a gene involved in various pathways and processes, including positive regulation of tumor necrosis factor (TNF) production, innate immune response-activating signal transduction, positive regulation of the innate immune response, and the biosynthesis of type I interferon (0.001

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Wang T,Yang J,Ji X,Chu M,Zhang R,Dai J,Jin G,Hu Z,Shen H,Ni C

doi

10.1016/j.toxlet.2014.10.028

subject

Has Abstract

pub_date

2015-01-05 00:00:00

pages

284-92

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(14)01410-6

journal_volume

232

pub_type

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