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

Publication ,  Journal Article
Wang, L; Pittman, KJ; Barker, JR; Salinas, RE; Stanaway, IB; Williams, GD; Carroll, RJ; Balmat, T; Ingham, A; Gopalakrishnan, AM; Gibbs, KD ...
Published in: Cell Host Microbe
August 8, 2018

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.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

August 8, 2018

Volume

24

Issue

2

Start / End Page

308 / 323.e6

Location

United States

Related Subject Headings

  • Web Browser
  • Transcription Factors
  • Risk Factors
  • Phenotype
  • Nerve Tissue Proteins
  • Inflammatory Bowel Diseases
  • Infections
  • Immunology
  • Humans
  • Hepatitis, Viral, Human
 

Citation

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Wang, L., Pittman, K. J., Barker, J. R., Salinas, R. E., Stanaway, I. B., Williams, G. D., … Ko, D. C. (2018). An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease. Cell Host Microbe, 24(2), 308-323.e6. https://doi.org/10.1016/j.chom.2018.07.007
Wang, Liuyang, Kelly J. Pittman, Jeffrey R. Barker, Raul E. Salinas, Ian B. Stanaway, Graham D. Williams, Robert J. Carroll, et al. “An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease.Cell Host Microbe 24, no. 2 (August 8, 2018): 308-323.e6. https://doi.org/10.1016/j.chom.2018.07.007.
Wang L, Pittman KJ, Barker JR, Salinas RE, Stanaway IB, Williams GD, et al. An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease. Cell Host Microbe. 2018 Aug 8;24(2):308-323.e6.
Wang, Liuyang, et al. “An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease.Cell Host Microbe, vol. 24, no. 2, Aug. 2018, pp. 308-323.e6. Pubmed, doi:10.1016/j.chom.2018.07.007.
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. An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease. Cell Host Microbe. 2018 Aug 8;24(2):308-323.e6.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

August 8, 2018

Volume

24

Issue

2

Start / End Page

308 / 323.e6

Location

United States

Related Subject Headings

  • Web Browser
  • Transcription Factors
  • Risk Factors
  • Phenotype
  • Nerve Tissue Proteins
  • Inflammatory Bowel Diseases
  • Infections
  • Immunology
  • Humans
  • Hepatitis, Viral, Human