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

Date
2018-08
Authors
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
eMERGE Network
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
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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.
Type
Journal article
Subject
eMERGE Network
Cell Line
Humans
Hepatitis, Viral, Human
Inflammatory Bowel Diseases
Genetic Predisposition to Disease
Nerve Tissue Proteins
Transcription Factors
Antibodies, Monoclonal
Cytokines
Data Collection
Risk Factors
DNA Mutational Analysis
Computational Biology
DNA Replication
Phenotype
Genome, Human
Databases, Genetic
Chemokine CXCL10
Genetic Variation
Genome-Wide Association Study
Electronic Health Records
Genetic Pleiotropy
Web Browser
Infections
Permalink
https://hdl.handle.net/10161/24734
Published Version (Please cite this version)
10.1016/j.chom.2018.07.007
Publication Info
Wang, Liuyang; Pittman, Kelly J; Barker, Jeffrey R; Salinas, Raul E; Stanaway, Ian B; Williams, Graham D; ... Ko, Dennis C (2018). An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease. Cell host & microbe, 24(2). pp. 308-323.e6. 10.1016/j.chom.2018.07.007. Retrieved from https://hdl.handle.net/10161/24734.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Mark DeLong

Adjunct Instructor in the Duke Initiative for Science & Society
Horner

Stacy M. Horner

Associate Professor in Integrative Immunobiology
Ko

Dennis Ko

Associate Professor in Molecular Genetics and Microbiology
Using Pathogens to Decipher Genetic Variation Connecting Cell Biology and Disease SusceptibilityDespite improvements in public health, advancements in vaccines, and the development of many classes of antibiotics, infectious disease is still responsible for over a quarter of all deaths worldwide. However, even for the most devastating of pandemics, individuals demonstrate a large variability in the severity of infection. The long-term goal of the lab is to understand the ge

Soo Chan Lee

Assistant Research Professor in Molecular Genetics and Microbiology
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Salinas

Raul Salinas

Research Associate, Senior
Valdivia

Raphael H. Valdivia

Nanaline H. Duke Distinguished Professor of Molecular Genetics and Microbiology
My laboratory is interested in microbes that influence human health, both in the context of host-pathogen and host-commensal interactions. For many pathogens, and certainly for most commensal microbes, we have an incomplete molecular understanding of how host and microbial factors contribute to health and disease. My research group focuses on two experimental systems: Chlamydia trachomatis infections are responsible for the bulk of sexually transmitted bacte
Wang

Liuyang Wang

Assistant Research Professor of Molecular Genetics and Microbiology
Alphabetical list of authors with Scholars@Duke profiles.
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