Efficient multiple-trait association and estimation of genetic correlation using the matrix-variate linear mixed model

Genetics
Nicholas A Furlotte, Eleazar Eskin

Abstract

Multiple-trait association mapping, in which multiple traits are used simultaneously in the identification of genetic variants affecting those traits, has recently attracted interest. One class of approaches for this problem builds on classical variance component methodology, utilizing a multitrait version of a linear mixed model. These approaches both increase power and provide insights into the genetic architecture of multiple traits. In particular, it is possible to estimate the genetic correlation, which is a measure of the portion of the total correlation between traits that is due to additive genetic effects. Unfortunately, the practical utility of these methods is limited since they are computationally intractable for large sample sizes. In this article, we introduce a reformulation of the multiple-trait association mapping approach by defining the matrix-variate linear mixed model. Our approach reduces the computational time necessary to perform maximum-likelihood inference in a multiple-trait model by utilizing a data transformation. By utilizing a well-studied human cohort, we show that our approach provides more than a 10-fold speedup, making multiple-trait association feasible in a large population cohort on the gen...Continue Reading

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Citations

Apr 4, 2016·Genome Biology·Jong Wha J JooEleazar Eskin
Jun 14, 2016·American Journal of Human Genetics·Farhad HormozdiariEleazar Eskin
Jul 28, 2016·Cell Systems·Sean SimmonsBonnie Berger
Jun 23, 2018·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Regev SchweigerEran Halperin
Jun 28, 2019·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·Robin Thompson
Nov 3, 2017·Open Biology·Sophie Hackinger, Eleftheria Zeggini
Feb 6, 2020·Genetics·Willem KruijerFred A van Eeuwijk
Dec 20, 2018·Animals : an Open Access Journal From MDPI·Wengang ZhangYan Chen
Jul 25, 2015·Genetics·Daniel GianolaDaniel Sorensen
May 28, 2019·Frontiers in Genetics·Deborah WeighillDaniel Jacobson
Mar 17, 2017·Behavior Genetics·Brad VerhulstMichael C Neale
Aug 17, 2016·Genetics·Daniel J SchaidJason P Sinnwell
Aug 18, 2020·The Annals of Applied Statistics·Wanghuan ChuMatthew Reimherr
May 24, 2020·Neurobiology of Disease·Eftychia BellouValentina Escott-Price
Sep 7, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Pushpendra K Gupta

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