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Multivariate estimation of factor structures of complex traits using SNP-based genomic relationships.

Published version
Peer-reviewed

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Authors

Slob, Eric AW 
Groenen, Patrick JF 
Rietveld, Cornelius A 

Abstract

BACKGROUND: Heritability and genetic correlation can be estimated from genome-wide single-nucleotide polymorphism (SNP) data using various methods. We recently developed multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) for statistically and computationally efficient estimation of SNP-based heritability ([Formula: see text]) and genetic correlation ([Formula: see text]) across many traits in large datasets. Here, we extend MGREML by allowing it to fit and perform tests on user-specified factor models, while preserving the low computational complexity. RESULTS: Using simulations, we show that MGREML yields consistent estimates and valid inferences for such factor models at low computational cost (e.g., for data on 50 traits and 20,000 individuals, a saturated model involving 50 [Formula: see text]'s, 1225 [Formula: see text]'s, and 50 fixed effects is estimated and compared to a restricted model in less than one hour on a single notebook with two 2.7 GHz cores and 16 GB of RAM). Using repeated measures of height and body mass index from the US Health and Retirement Study, we illustrate the ability of MGREML to estimate a factor model and test whether it fits the data better than a nested model. The MGREML tool, the simulation code, and an extensive tutorial are freely available at https://github.com/devlaming/mgreml/ . CONCLUSION: MGREML can now be used to estimate multivariate factor structures and perform inferences on such factor models at low computational cost. This new feature enables simple structural equation modeling using MGREML, allowing researchers to specify, estimate, and compare genetic factor models of their choosing using SNP data.

Description

Funder: NIHR Cambridge BRC

Keywords

Software, SNP heritability, Genetic correlation, GREML, Genetic factor model, Genomic SEM

Journal Title

BMC Bioinformatics

Conference Name

Journal ISSN

1471-2105
1471-2105

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
European Research Council (Starting Grant 946647 GEPSI)
National Institute on Aging (Grant NIA U01AG009740)