Two-variance-component model improves genetic prediction in family datasets

Tucker, George, Loh, Po-Ru, MacLeod, Iona M., Hayes, Ben J., Goddard, Michael E., Berger, Bonnie and Price, Alkes L. (2015) Two-variance-component model improves genetic prediction in family datasets. American Journal of Human Genetics, 97 5: 677-690. doi:10.1016/j.ajhg.2015.10.002

Author Tucker, George
Loh, Po-Ru
MacLeod, Iona M.
Hayes, Ben J.
Goddard, Michael E.
Berger, Bonnie
Price, Alkes L.
Title Two-variance-component model improves genetic prediction in family datasets
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 1537-6605
Publication date 2015-11-05
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2015.10.002
Open Access Status Not Open Access
Volume 97
Issue 5
Start page 677
End page 690
Total pages 14
Place of publication Cambridge, United States
Publisher Cell Press
Language eng
Formatted abstract
Genetic prediction based on either identity by state (IBS) sharing or pedigree information has been investigated extensively with best linear unbiased prediction (BLUP) methods. Such methods were pioneered in plant and animal-breeding literature and have since been applied to predict human traits, with the aim of eventual clinical utility. However, methods to combine IBS sharing and pedigree information for genetic prediction in humans have not been explored. We introduce a two-variance-component model for genetic prediction: one component for IBS sharing and one for approximate pedigree structure, both estimated with genetic markers. In simulations using real genotypes from the Candidate-gene Association Resource (CARe) and Framingham Heart Study (FHS) family cohorts, we demonstrate that the two-variance-component model achieves gains in prediction r2 over standard BLUP at current sample sizes, and we project, based on simulations, that these gains will continue to hold at larger sample sizes. Accordingly, in analyses of four quantitative phenotypes from CARe and two quantitative phenotypes from FHS, the two-variance-component model significantly improves prediction r2 in each case, with up to a 20% relative improvement. We also find that standard mixed-model association tests can produce inflated test statistics in datasets with related individuals, whereas the two-variance-component model corrects for inflation.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Alliance for Agriculture and Food Innovation
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