A Likelihood-Based Approach to Mixed Modeling with Ambiguity in Cluster Identifiers

This manuscript describes a novel, linear mixed-effects model–fitting technique for the setting in which correlated data indicators are not completely observed. Mixed modeling is a useful analytical tool for characterizing genotype–phenotype associations among multiple potentially informative genetic loci. This approach involves grouping individuals into genetic clusters, where individuals in the same cluster have similar or identical multilocus genotypes. In haplotype-based investigations of unrelated individuals, corresponding cluster assignments are unobservable since the alignment of alleles within chromosomal copies is not generally observed. We derive an expectation conditional maximization approach to estimation in the mixed modeling setting, where cluster assignments are ambiguous. The approach has broad relevance to the analysis of data with missing correlated data identifiers. An example is provided based on data arising from a cohort of human immunodeficiency virus type-1–infected individuals at risk for antiretroviral therapy–associated dyslipidemia