With the advent of high throughput genetic data, there have been attempts to estimate heritability from genome-wide SNP data on a cohort of distantly related individuals using linear mixed model (LMM). Fitting such an LMM in a large scale cohort study, however, is tremendously challenging due to its high dimensional linear algebraic operations. In this paper, we propose a new method named PredLMM approximating the aforementioned LMM motivated by the concepts of genetic coalescence and Gaussian predictive process. PredLMM has substantially better computational complexity than most of the existing LMM based methods and thus, provides a fast alternative for estimating heritability in large scale cohort studies. Theoretically, we show that under a model of genetic coalescence, the limiting form of our approximation is the celebrated predictive process approximation of large Gaussian process likelihoods that has well-established accuracy standards. We illustrate our approach with extensive simulation studies and use it to estimate the heritability of multiple quantitative traits from the UK Biobank cohort.
Bibliographical noteFunding Information:
This study is supported in part by the National Institutes of Health/National Institute on Drug Abuse grants 5R01DA033958-02 (SB) and 1R21DA046188-01A1 (SB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported within this paper.
Copyright: © 2022 Seal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural