From SNPs to Genes: Disease Association at the Gene Level

被引：57

作者：

Lehne, Benjamin ^{[1
]}

Lewis, Cathryn M. ^{[1
,2
]}

Schlitt, Thomas ^{[1
]}

机构：

[1] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England

[2] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England

来源：

PLOS ONE | 2011年 / 6卷 / 06期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; ALPHA-DYSTROGLYCAN; PATHWAY ANALYSIS; COMMON DISEASES; CROHNS-DISEASE; SUSCEPTIBILITY; IDENTIFICATION; VARIANTS; MUTATION; RECEPTOR;

D O I：

10.1371/journal.pone.0020133

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Interpreting Genome-Wide Association Studies (GWAS) at a gene level is an important step towards understanding the molecular processes that lead to disease. In order to incorporate prior biological knowledge such as pathways and protein interactions in the analysis of GWAS data it is necessary to derive one measure of association for each gene. We compare three different methods to obtain gene-wide test statistics from Single Nucleotide Polymorphism (SNP) based association data: choosing the test statistic from the most significant SNP; the mean test statistics of all SNPs; and the mean of the top quartile of all test statistics. We demonstrate that the gene-wide test statistics can be controlled for the number of SNPs within each gene and show that all three methods perform considerably better than expected by chance at identifying genes with confirmed associations. By applying each method to GWAS data for Crohn's Disease and Type 1 Diabetes we identified new potential disease genes.

引用

页数：10

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