Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.

Détails

Ressource 1Télécharger: BIB_50526236BCA7.P001.pdf (1455.52 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_50526236BCA7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.
Périodique
Plos Computational Biology
Auteur(s)
Lamparter D., Marbach D., Rueedi R., Kutalik Z., Bergmann S.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Statut éditorial
Publié
Date de publication
2016
Volume
12
Numéro
1
Pages
e1004714
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Integrating single nucleotide polymorphism (SNP) p-values from genome-wide association studies (GWAS) across genes and pathways is a strategy to improve statistical power and gain biological insight. Here, we present Pascal (Pathway scoring algorithm), a powerful tool for computing gene and pathway scores from SNP-phenotype association summary statistics. For gene score computation, we implemented analytic and efficient numerical solutions to calculate test statistics. We examined in particular the sum and the maximum of chi-squared statistics, which measure the strongest and the average association signals per gene, respectively. For pathway scoring, we use a modified Fisher method, which offers not only significant power improvement over more traditional enrichment strategies, but also eliminates the problem of arbitrary threshold selection inherent in any binary membership based pathway enrichment approach. We demonstrate the marked increase in power by analyzing summary statistics from dozens of large meta-studies for various traits. Our extensive testing indicates that our method not only excels in rigorous type I error control, but also results in more biologically meaningful discoveries.
Mots-clé
Algorithms, Computational Biology/methods, Genome-Wide Association Study/methods, HapMap Project, Humans, Phenotype, Polymorphism, Single Nucleotide/genetics, Software
Pubmed
Web of science
Création de la notice
11/02/2016 17:32
Dernière modification de la notice
03/03/2018 17:08
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