Methods for testing association between uncertain genotypes and quantitative traits.
Détails
Demande d'une copie Sous embargo indéterminé.
Accès restreint UNIL
Etat: Public
Version: de l'auteur⸱e
Accès restreint UNIL
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_3B14FBDAAC90
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Methods for testing association between uncertain genotypes and quantitative traits.
Périodique
Biostatistics
ISSN
1468-4357 (Electronic)
ISSN-L
1465-4644
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
12
Numéro
1
Pages
1-17
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Interpretability and power of genome-wide association studies can be increased by imputing unobserved genotypes, using a reference panel of individuals genotyped at higher marker density. For many markers, genotypes cannot be imputed with complete certainty, and the uncertainty needs to be taken into account when testing for association with a given phenotype. In this paper, we compare currently available methods for testing association between uncertain genotypes and quantitative traits. We show that some previously described methods offer poor control of the false-positive rate (FPR), and that satisfactory performance of these methods is obtained only by using ad hoc filtering rules or by using a harsh transformation of the trait under study. We propose new methods that are based on exact maximum likelihood estimation and use a mixture model to accommodate nonnormal trait distributions when necessary. The new methods adequately control the FPR and also have equal or better power compared to all previously described methods. We provide a fast software implementation of all the methods studied here; our new method requires computation time of less than one computer-day for a typical genome-wide scan, with 2.5 M single nucleotide polymorphisms and 5000 individuals.
Mots-clé
Data Interpretation, Statistical, Genetic Variation/genetics, Genome-Wide Association Study/methods, Genotype, Humans, Models, Genetic, Polymorphism, Single Nucleotide/genetics, Quantitative Trait, Heritable
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/01/2011 10:45
Dernière modification de la notice
20/08/2019 13:30