CERAMIC: Case-Control Association Testing in Samples with Related Individuals, Based on Retrospective Mixed Model Analysis with Adjustment for Covariates

PLoS Genetics
Sheng ZhongMary Sara McPeek

Abstract

We consider the problem of genetic association testing of a binary trait in a sample that contains related individuals, where we adjust for relevant covariates and allow for missing data. We propose CERAMIC, an estimating equation approach that can be viewed as a hybrid of logistic regression and linear mixed-effects model (LMM) approaches. CERAMIC extends the recently proposed CARAT method to allow samples with related individuals and to incorporate partially missing data. In simulations, we show that CERAMIC outperforms existing LMM and generalized LMM approaches, maintaining high power and correct type 1 error across a wider range of scenarios. CERAMIC results in a particularly large power increase over existing methods when the sample includes related individuals with some missing data (e.g., when some individuals with phenotype and covariate information have missing genotype), because CERAMIC is able to make use of the relationship information to incorporate partially missing data in the analysis while correcting for dependence. Because CERAMIC is based on a retrospective analysis, it is robust to misspecification of the phenotype model, resulting in better control of type 1 error and higher power than that of prospective ...Continue Reading

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Citations

Jan 4, 2019·Briefings in Functional Genomics·Denis AwanyEmile R Chimusa
Jun 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Miaoyan WangJoy Bergelson
Jun 12, 2021·Archives of Virology·Annika AntonssonAdele C Green

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Software Mentioned

CERAMIC
LIN
EMMAX
MASTOR
MQLS
GMMAT
CARAT
LOG
GEMMA

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