Transformation of Summary Statistics from Linear Mixed Model Association on All-or-None Traits to Odds Ratio.

Details

Serval ID
serval:BIB_89C078E7C44D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transformation of Summary Statistics from Linear Mixed Model Association on All-or-None Traits to Odds Ratio.
Journal
Genetics
Author(s)
Lloyd-Jones L.R., Robinson M.R., Yang J., Visscher P.M.
ISSN
1943-2631 (Electronic)
ISSN-L
0016-6731
Publication state
Published
Issued date
04/2018
Peer-reviewed
Oui
Volume
208
Number
4
Pages
1397-1408
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Genome-wide association studies (GWAS) have identified thousands of loci that are robustly associated with complex diseases. The use of linear mixed model (LMM) methodology for GWAS is becoming more prevalent due to its ability to control for population structure and cryptic relatedness and to increase power. The odds ratio (OR) is a common measure of the association of a disease with an exposure ( <i>e.g.</i> , a genetic variant) and is readably available from logistic regression. However, when the LMM is applied to all-or-none traits it provides estimates of genetic effects on the observed 0-1 scale, a different scale to that in logistic regression. This limits the comparability of results across studies, for example in a meta-analysis, and makes the interpretation of the magnitude of an effect from an LMM GWAS difficult. In this study, we derived transformations from the genetic effects estimated under the LMM to the OR that only rely on summary statistics. To test the proposed transformations, we used real genotypes from two large, publicly available data sets to simulate all-or-none phenotypes for a set of scenarios that differ in underlying model, disease prevalence, and heritability. Furthermore, we applied these transformations to GWAS summary statistics for type 2 diabetes generated from 108,042 individuals in the UK Biobank. In both simulation and real-data application, we observed very high concordance between the transformed OR from the LMM and either the simulated truth or estimates from logistic regression. The transformations derived and validated in this study improve the comparability of results from prospective and already performed LMM GWAS on complex diseases by providing a reliable transformation to a common comparative scale for the genetic effects.
Keywords
Algorithms, Computer Simulation, Diabetes Mellitus, Type 2/genetics, Diabetes Mellitus, Type 2/metabolism, Genetic Association Studies, Genome-Wide Association Study, Humans, Linear Models, Models, Genetic, Multifactorial Inheritance, Odds Ratio, Quantitative Trait, Heritable, OR, complex diseases, genome-wide association studies, linear mixed models, summary statistics
Pubmed
Web of science
Create date
15/02/2018 21:14
Last modification date
20/08/2019 15:48
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