| Literature DB >> 30092202 |
Liuyang Wang1, Kelly J Pittman1, Jeffrey R Barker1, Raul E Salinas1, Ian B Stanaway2, Graham D Williams1, Robert J Carroll3, Tom Balmat4, Andy Ingham5, Anusha M Gopalakrishnan1, Kyle D Gibbs1, Alejandro L Antonia1, Joseph Heitman6, Soo Chan Lee7, Gail P Jarvik8, Joshua C Denny3, Stacy M Horner6, Mark R DeLong5, Raphael H Valdivia1, David R Crosslin2, Dennis C Ko9.
Abstract
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.Entities:
Keywords: CXCL10; ZBTB20; eldelumab; electronic medical record; genome-wide association study; heritability; immune quantitative trait locus; lymphoblastoid cell line; phewas; pleiotropy
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Year: 2018 PMID： 30092202 PMCID： PMC6093297 DOI： 10.1016/j.chom.2018.07.007
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023