An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease.
Pathogens have been a strong driving force for natural selection. Therefore, understanding how human genetic differences impact infection-related cellular traits can mechanistically link genetic variation to disease susceptibility. Here we report the Hi-HOST Phenome Project (H2P2): a catalog of cellular genome-wide association studies (GWAS) comprising 79 infection-related phenotypes in response to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome-wide significance for infection-associated phenotypes ranging from pathogen replication to cytokine production. We combined H2P2 with clinical association data from patients to identify a SNP near CXCL10 as a risk factor for inflammatory bowel disease. A SNP in the transcriptional repressor ZBTB20 demonstrated pleiotropy, likely through suppression of multiple target genes, and was associated with viral hepatitis. These data are available on a web portal to facilitate interpreting human genome variation through the lens of cell biology and should serve as a rich resource for the research community.
Wang, L; Pittman, KJ; Barker, JR; Salinas, RE; Stanaway, IB; Williams, GD; Carroll, RJ; Balmat, T; Ingham, A; Gopalakrishnan, AM; Gibbs, KD; Antonia, AL; eMERGE Network, ; Heitman, J; Lee, SC; Jarvik, GP; Denny, JC; Horner, SM; DeLong, MR; Valdivia, RH; Crosslin, DR; Ko, DC
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