Integrating Molecular QTL Data into Genome-wide Genetic Association Analysis: Probabilistic Assessment of Enrichment and Colocalization
We propose a novel statistical framework for integrating genetic data from molecular quantitative trait loci (QTL) mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of association signals. We introduce a natural Bayesian hierarchical model that treats the latent association status of molecular QTLs as SNP-level annotations for candidate SNPs for complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and the analysis of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals, which is analogous to the power calculation in genetic association studies. Using this utility, we further illustrate the importance of enrichment analysis on the ability of discovering colocalized signals and the potential limitations of currently available molecular QTL data.
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