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

TitleMultivariate estimation of factor structures of complex traits using SNP-based genomic relationships.
Publication TypeJournal Article
Year of Publication2022
Authorsde Vlaming, R, Slob, EAW, Groenen, PJF, Rietveld, CA
JournalBMC Bioinformatics
Volume23
Issue1
Pagination305
ISSN Number1471-2105
KeywordsGenome, Genome-Wide Association Study, Genomics, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide
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.

DOI10.1186/s12859-022-04835-3
Citation Key12579
PubMed ID35896974
PubMed Central IDPMC9327374
Grant ListStarting Grant 946647 GEPSI / ERC_ / European Research Council / International
Grant NIA U01AG009740 / AG / NIA NIH HHS / United States