A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits.

Détails

Ressource 1Télécharger: 35921544_BIB_C0A2EB45D9AE.pdf (767.62 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_C0A2EB45D9AE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits.
Périodique
Molecular biology and evolution
Auteur⸱e⸱s
Nadeau S., Thorball C.W., Kouyos R., Günthard H.F., Böni J., Yerly S., Perreau M., Klimkait T., Rauch A., Hirsch H.H., Cavassini M., Vernazza P., Bernasconi E., Fellay J., Mitov V., Stadler T.
Collaborateur⸱rice⸱s
Swiss HIV Cohort Study (SHCS)
Contributeur⸱rice⸱s
Abela I., Aebi-Popp K., Anagnostopoulos A., Battegay M., Bernasconi E., Braun D.L., Bucher H.C., Calmy A., Cavassini M., Ciuffi A., Dollenmaier G., Egger M., Elzi L., Fehr J., Fellay J., Furrer H., Fux C.A., Günthard H.F., Hachfeld A., Haerry D., Hasse B., Hirsch H.H., Hoffmann M., Hösli I., Huber M., Kahlert C.R., Kaiser L., Keiser O., Klimkait T., Kouyos R.D., Kovari H., Kusejko K., Martinetti G., Martinez T.B., Marzolini C., Metzner K.J., Müller N., Nemeth J., Nicca D., Paioni P., Pantaleo G., Perreau M., Rauch A., Schmid P., Speck R., Stöckle M., Tarr P., Trkola A., Wandeler G., Yerly S.
ISSN
1537-1719 (Electronic)
ISSN-L
0737-4038
Statut éditorial
Publié
Date de publication
03/08/2022
Peer-reviewed
Oui
Volume
39
Numéro
8
Pages
msac163
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Infectious diseases are particularly challenging for genome-wide association studies (GWAS) because genetic effects from two organisms (pathogen and host) can influence a trait. Traditional GWAS assume individual samples are independent observations. However, pathogen effects on a trait can be heritable from donor to recipient in transmission chains. Thus, residuals in GWAS association tests for host genetic effects may not be independent due to shared pathogen ancestry. We propose a new method to estimate and remove heritable pathogen effects on a trait based on the pathogen phylogeny prior to host GWAS, thus restoring independence of samples. In simulations, we show this additional step can increase GWAS power to detect truly associated host variants when pathogen effects are highly heritable, with strong phylogenetic correlations. We applied our framework to data from two different host-pathogen systems, HIV in humans and X. arboricola in A. thaliana. In both systems, the heritability and thus phylogenetic correlations turn out to be low enough such that qualitative results of GWAS do not change when accounting for the pathogen shared ancestry through a correction step. This means that previous GWAS results applied to these two systems should not be biased due to shared pathogen ancestry. In summary, our framework provides additional information on the evolutionary dynamics of traits in pathogen populations and may improve GWAS if pathogen effects are highly phylogenetically correlated amongst individuals in a cohort.
Mots-clé
Communicable Diseases/genetics, Genome-Wide Association Study/methods, Humans, Phenotype, Phylogeny, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, genome-wide association study, heritability, infectious disease, phylogenetic mixed model
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/08/2022 14:17
Dernière modification de la notice
23/01/2024 8:33
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