Titre
Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Lamparter, D.
Auteure/Auteur
Marbach, D.
Auteure/Auteur
Rueedi, R.
Auteure/Auteur
Kutalik, Z.
Auteure/Auteur
Bergmann, S.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1553-7358
Statut éditorial
Publié
Date de publication
2016
Volume
12
Numéro
1
Première page
e1004714
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
PID Serval
serval:BIB_50526236BCA7
PMID
Open Access
Oui
Date de création
2016-02-11T15:32:17.363Z
Date de création dans IRIS
2025-05-20T17:30:36Z
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Nom
BIB_50526236BCA7.P001.pdf
Version du manuscrit
published
Taille
1.42 MB
Format
Adobe PDF
PID Serval
serval:BIB_50526236BCA7.P001
URN
urn:nbn:ch:serval-BIB_50526236BCA71
Somme de contrôle
(MD5):2c9ee1ad56f48574a5b7d2a19ba6c824