Two-way mixed-effects methods for joint association analysis using both host and pathogen genomes

Proceedings of the National Academy of Sciences of the United States of America
Miaoyan WangJoy Bergelson

Abstract

Infectious diseases are often affected by specific pairings of hosts and pathogens and therefore by both of their genomes. The integration of a pair of genomes into genome-wide association mapping can provide an exquisitely detailed view of the genetic landscape of complex traits. We present a statistical method, ATOMM (Analysis with a Two-Organism Mixed Model), that maps a trait of interest to a pair of genomes simultaneously; this method makes use of whole-genome sequence data for both host and pathogen organisms. ATOMM uses a two-way mixed-effect model to test for genetic associations and cross-species genetic interactions while accounting for sample structure including interactions between the genetic backgrounds of the two organisms. We demonstrate the applicability of ATOMM to a joint association study of quantitative disease resistance (QDR) in the Arabidopsis thaliana-Xanthomonas arboricola pathosystem. Our method uncovers a clear host-strain specificity in QDR and provides a powerful approach to identify genetic variants on both genomes that contribute to phenotypic variation.

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Citations

Nov 18, 2018·The Plant Journal : for Cell and Molecular Biology·Maricris L ZaidemMichael D Purugganan
Nov 23, 2018·The Plant Journal : for Cell and Molecular Biology·Kathleen BeilsmithJoy Bergelson
Feb 9, 2019·PLoS Genetics·Daniel E Runcie, Lorin Crawford
Apr 11, 2019·Molecular Biology and Evolution·Léa FrachonFabrice Roux
Aug 15, 2019·The Plant Journal : for Cell and Molecular Biology·Dawn ChiniquyShauna Somerville
Nov 16, 2019·Human Genetics·Jacques Fellay, Vincent Pedergnana
Aug 30, 2020·Nature Reviews. Genetics·Dieter Ebert, Peter D Fields
Mar 8, 2019·Viruses·Cas RetelPhiline G D Feulner
Sep 28, 2020·The New Phytologist·Henri DesaintRichard Berthomé
Nov 13, 2020·Phytopathology·Christina StraubHonour C McCann
Nov 30, 2019·Trends in Genetics : TIG·Nandita R Garud, Katherine S Pollard
Jan 26, 2021·Computational and Structural Biotechnology Journal·Nikhil Kumar SinghDaniel Croll
May 27, 2021·Molecular Ecology·Hanna MärkleAurélien Tellier
May 16, 2021·Molecular Plant·Amber N HafeezBrande B H Wulff

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