The genetic basis of infectious disease (ID) risk and severity has been relatively
A schematic diagram illustrating our study design and the reference resource we provide 130 can be found in Figure The ID-associated genes tend to be less tissue-specific (i.e., more ubiquitously 212 expressed) than the remaining genes ( Figure S1A , Mann Whitney U test on the  statistic, p = 213 7.5x10 -4 ), possibly reflecting the multi-tissue PrediXcan approach we implemented, which 214 prioritizes genes with multi-tissue support to improve statistical power, but also the genes' 215 pleiotropic potential. We hypothesized that tissue expression profiling of ID-associated genes 216 can provide additional insights into disease etiologies and mechanisms. For example, the 217 intestinal infection associated gene NDUFA4 is expressed in a broad set of tissues, including 218 the alimentary canal, but displays relatively low expression in whole blood ( Figure S1B ). In 219 addition, TOR4A, the most significant association with bacterial pneumonia (Table 1) Table 5 ). These data identify specific molecular mechanisms across ID traits with critical 239 regulatory roles (e.g., protein modifications) in host response among the ID-associated genes.
We tested the hypothesis that distinct infectious agents exploit common pathways to find 241 a compatible intracellular niche in the host, potentially implicating shared genetic risk factors.
Notably, 64 of the 70 ID-associated genes ( 
Notably, we identified an enrichment (FDR = 9.68x10 -3 ) for a highly conserved motif Figure 7A ). In addition, we identified significantly more replicated SNP 
Our study provides a reference atlas of genetic variants and genetically-determined 
Integrating predicted transcriptome from multiple tissues improves association detection. PLoS
Genet 15, e1007889. 