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

Cell Host Microbe. 2018 Aug 8;24(2):308-323.e6. doi: 10.1016/j.chom.2018.07.007.


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.

Keywords: CXCL10; ZBTB20; eldelumab; electronic medical record; genome-wide association study; heritability; immune quantitative trait locus; lymphoblastoid cell line; phewas; pleiotropy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Cell Line
  • Chemokine CXCL10 / genetics
  • Computational Biology / methods*
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA Mutational Analysis
  • DNA Replication
  • Data Collection
  • Databases, Genetic
  • Electronic Health Records
  • Genetic Pleiotropy
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genome, Human*
  • Genome-Wide Association Study / instrumentation
  • Genome-Wide Association Study / methods*
  • Hepatitis, Viral, Human
  • Humans
  • Infections*
  • Inflammatory Bowel Diseases
  • Nerve Tissue Proteins / genetics
  • Phenotype*
  • Risk Factors
  • Transcription Factors / genetics
  • Web Browser


  • Antibodies, Monoclonal
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Cytokines
  • Nerve Tissue Proteins
  • Transcription Factors
  • ZBTB20 protein, human
  • eldelumab