The SMR method was detailed in the previous paper [22]. In brief, SMR applies the principles of Mendelian randomization (MR) [37,38] to jointly analyze GWAS and eQTL summary statistics in order to test for association between gene expression and a trait due to a shared variant at a locus. In this study, the phenotypic trait is the outcome (Y), gene expression is the exposure (X), and the top cis-eQTL that is strongly associated with gene expression is used as the instrumental variable (Z). Equivalently, it is an analysis to test whether the effect of Z on Y is mediated by X (a model of Z → X → Y). The SMR software was downloaded from http://cnsgenomics.com/software/smr/.
