We used S-PrediXcan [23] to predict gene expression and the mediating effects of variation on gene expression on PAU. Forty-eight tissues from GTEx [16] release v7 and whole blood samples from the Depression Genes and Networks study (DGN) [24] were analyzed as reference transcriptomes (Supplementary Table 9). After Bonferroni correction, 103 gene-tissue associations were significant, representing 39 different genes, some of which were identified in multiple tissues (Supplementary Table 10). For example, C1QTNF4 (C1q and TNF Related 4) was detected in 18 tissues, including brain, gastrointestinal, adipose, and liver. None of the four significant alcohol dehydrogenase genes (ADH1A, ADH1B, ADH4, and ADH5) was associated with expression in brain tissue, but they were associated with expression in other tissues -- adipose, thyroid, gastrointestinal and heart. These cross-tissue associations indicate that there are widespread functional consequences of PAU-risk-associated genetic variation at the expression level.
