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Motivated by genome-wide association studies, we consider a standard linear model with one additional random effect in situations where many predictors have been collected on the same subjects and each predictor is analyzed separately. Three novel contributions are (1) a transformation between the linear and log-odds scales which is accurate for the important genetic case of small effect sizes; (2) a likelihood-maximization algorithm that is an order of magnitude faster than the previously published approaches; and (3) efficient methods for computing marginal likelihoods which allow Bayesian model comparison. The methodology has been successfully applied to a large-scale association study of multiple sclerosis including over 20,000 individuals and 500,000 genetic variants. © 2013 Institute of Mathematical Statistics.

Original publication




Journal article


Annals of Applied Statistics

Publication Date





369 - 390