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Abstract:
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The commonly used statistical methods in medical research generally assume patients arise from one homogeneous population. However, it is well known that common and complex human diseases usually have heterogeneous disease etiology, which usually involves interplay of multiple genetic and environmental factors, leading to latent population substructure. Genome-wide association studies (GWAS) is a useful tool to uncover genetic association with disease of interest, while linkage analysis is a commonly used method to identify statistical association between the inheritance of a human disease and inheritance of marker loci. In this paper, we propose a likelihood ratio test under genetic heterogeneity for genome-wide linkage analysis using family data. We derive a closed-form formula for the LRT test statistic and provide explicit asymptotic null distribution. Simulation studies indicate the test has proper type I error and good power under genetic heterogeneity. In order to simplify application of the proposed method for non-statisticians, we develop an R package gLRTH to implement our method.
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