Details

Autor(en) / Beteiligte

• Wang, Liuyang
• Pittman, Kelly J.
• Barker, Jeffrey R.
• Salinas, Raul E.
• Stanaway, Ian B.
• Williams, Graham D.
• Carroll, Robert J.
• Balmat, Tom
• Ingham, Andy
• Gopalakrishnan, Anusha M.
• Gibbs, Kyle D.
• Antonia, Alejandro L.
• Heitman, Joseph
• Lee, Soo Chan
• Jarvik, Gail P.
• Denny, Joshua C.
• Horner, Stacy M.
• DeLong, Mark R.
• Valdivia, Raphael H.
• Crosslin, David R.
• Ko, Dennis C.

Titel

An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease

Ist Teil von

• Cell host & microbe, 2018-08, Vol.24 (2), p.308-323.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Heritable variation in 79 cellular responses to infection with 8 pathogens was assessed•Phenotypes segregate in biologically meaningful clusters•17 significant genome-wide associations with infection phenotypes were identified•Integration with clinical GWAS revealed SNPs associated with IBD and hepatitis Approaches are needed for a deeper understanding of how human genetics impacts disease susceptibility. Wang et al. present a catalog of cellular genome-wide association studies comprising 79 phenotypes in response to 8 pathogens. Combining this with clinical association data and experimental validation revealed mechanisms and connections to disease.