{"doi":"10.1101/202325","title":"An atlas of genetic variation for linking pathogen-induced cellular traits to human disease","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with disease. To facilitate moving from associations to disease mechanisms, we leveraged the role of pathogens in shaping human evolution with the Hi-HOST Phenome Project (H2P2): a catalog of cellular GWAS comprised of 79 phenotypes in response to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome-wide significance (p&lt;5×10\n                  <jats:sup>−8</jats:sup>\n                  ) for phenotypes ranging from pathogen replication to cytokine production. Combining H2P2 with clinical association data from the eMERGE Network and experimental validation revealed evidence for mechanisms of action and connections with diseases. We identified a SNP near\n                  <jats:italic>CXCL10</jats:italic>\n                  as a cis-cytokine-QTL and a new risk factor for inflammatory bowel disease. A SNP in\n                  <jats:italic>ZBTB20</jats:italic>\n                  demonstrated pleiotropy, partially mediated through NF\n                  <jats:italic>κ</jats:italic>\n                  B signaling, and was associated with viral hepatitis. Data are available in an H2P2 web portal to facilitate further interpreting human genome variation through the lens of cell biology.\n                </jats:p>","journal":null,"year":null,"id":629225,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":49.1,"corpus_rank":6797,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411015,"name":"Kelly J. Pittman","orcid":"0000-0003-1580-7889","position":1,"is_corresponding":false},{"id":1517927,"name":"Jeffrey R. Barker","orcid":null,"position":2,"is_corresponding":false},{"id":1629458,"name":"Raul E. Salinas","orcid":null,"position":3,"is_corresponding":false},{"id":279183,"name":"Ian B. Stanaway","orcid":"0000-0002-0783-0918","position":4,"is_corresponding":false},{"id":343902,"name":"Graham D. Williams","orcid":"0000-0003-3387-4356","position":5,"is_corresponding":false},{"id":251747,"name":"Robert J. Carroll","orcid":"0000-0003-3802-8183","position":6,"is_corresponding":false},{"id":1629459,"name":"Tom Balmat","orcid":null,"position":7,"is_corresponding":false},{"id":554912,"name":"Andy Ingham","orcid":null,"position":8,"is_corresponding":false},{"id":1629460,"name":"Anusha M. Gopalakrishnan","orcid":null,"position":9,"is_corresponding":false},{"id":901095,"name":"Kyle D. Gibbs","orcid":"0000-0001-6868-9519","position":10,"is_corresponding":false},{"id":411013,"name":"Alejandro L. Antonia","orcid":"0000-0003-4387-6398","position":11,"is_corresponding":false},{"id":53024,"name":"Joseph Heitman","orcid":"0000-0001-6369-5995","position":13,"is_corresponding":false},{"id":363283,"name":"Soo Chan Lee","orcid":"0000-0002-7792-5947","position":14,"is_corresponding":false},{"id":1629463,"name":"Gail P. Jarvick","orcid":null,"position":15,"is_corresponding":false},{"id":22022,"name":"Joshua C. Denny","orcid":"0000-0002-3049-7332","position":16,"is_corresponding":false},{"id":229072,"name":"Stacy M. Horner","orcid":"0000-0002-9351-7409","position":17,"is_corresponding":false},{"id":1629464,"name":"Mark R. Delong","orcid":null,"position":18,"is_corresponding":false},{"id":411018,"name":"Raphael H. Valdivia","orcid":"0000-0003-0961-073X","position":19,"is_corresponding":false},{"id":275126,"name":"David R. Crosslin","orcid":"0000-0003-3658-9059","position":20,"is_corresponding":false},{"id":411019,"name":"Dennis C. Ko","orcid":"0000-0002-0113-5981","position":21,"is_corresponding":false},{"id":411014,"name":"Liuyang Wang","orcid":"0000-0001-9556-2361","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An atlas of genetic variation for linking pathogen-induced cellular traits to human disease","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with disease. To facilitate moving from associations to disease mechanisms, we leveraged the role of pathogens in shaping human evolution with the Hi-HOST Phenome Project (H2P2): a catalog of cellular GWAS comprised of 79 phenotypes in response to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome-wide significance (p&lt;5×10\n                  <jats:sup>−8</jats:sup>\n                  ) for phenotypes ranging from pathogen replication to cytokine production. Combining H2P2 with clinical association data from the eMERGE Network and experimental validation revealed evidence for mechanisms of action and connections with diseases. We identified a SNP near\n                  <jats:italic>CXCL10</jats:italic>\n                  as a cis-cytokine-QTL and a new risk factor for inflammatory bowel disease. A SNP in\n                  <jats:italic>ZBTB20</jats:italic>\n                  demonstrated pleiotropy, partially mediated through NF\n                  <jats:italic>κ</jats:italic>\n                  B signaling, and was associated with viral hepatitis. Data are available in an H2P2 web portal to facilitate further interpreting human genome variation through the lens of cell biology.\n                </jats:p>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W2767087557","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5U01HG008657-07","title":"eMERGE IV Northwest: A partnership to evaluate the use of genomic information in the health care of diverse participants"},{"funder_name":"National Institutes of Health","grant_id":"5U01HG004438-04","title":"JH/CIDR Genotyping for Genome-Wide Association Studies"},{"funder_name":"National Institutes of Health","grant_id":"5R01AI118903-09","title":"HUMAN GENETIC VARIATION REGULATING SALMONELLA HOST-PATHOGEN INTERACTIONS AND DISEASE SUSCEPTIBILITY"},{"funder_name":"National Institutes of Health","grant_id":"5U01HG008679-04","title":"EMR-Linked Biobank for Translational Genomics"},{"funder_name":"National Institutes of Health","grant_id":"5U01HG008666-03","title":"Better Outcomes for Children: Promoting Excellence in Healthcare Genomics to Inform Policy"},{"funder_name":"National Institutes of Health","grant_id":"5U01HG008680-03","title":"Columbia GENIE (GENomic Integration with Ehr)"},{"funder_name":"National Institutes of Health","grant_id":"2R01AI118903-06A1","title":"HUMAN GENETIC VARIATION REGULATING SALMONELLA HOST-PATHOGEN INTERACTIONS AND DISEASE SUSCEPTIBILITY"},{"funder_name":"National Institutes of Health","grant_id":"5U19AI084044-03","title":"Chlamydial Pathogeneis in the Reproductive Tract"},{"funder_name":"National Institutes of Health","grant_id":"5U19AI084044-09","title":"Ecopathogenomics of sexually transmitted infections (EPSTI)"},{"funder_name":"National Institutes of Health","grant_id":"5U01HG008673-03","title":"Genomic Medicine at Northwestern: Discovery and Implementation"},{"funder_name":"National Institutes of Health","grant_id":"3U01HG008676-04S2","title":"EMERGE III CENTRAL SEQUENCING, GENOTYPING AND INTERPRETATION FACILITY"},{"funder_name":"National Institutes of Health","grant_id":"3U01HG006379-06S1","title":"EHR-based Genomic Discovery and Implementation"},{"funder_name":"National Institutes of Health","grant_id":"1U01HG008664-01","title":"DNA Sequencing Support for the eMERGE Network"},{"funder_name":"National Institutes of Health","grant_id":"3U01HG008672-03S1","title":"VGER, the Vanderbilt Genome-Electronic Records Project"},{"funder_name":"National Institutes of Health","grant_id":"3U01HG008684-04S1","title":"The Future of Genomics Medicine in Patient Care: Contributions from CHOP"},{"funder_name":"National Institutes of Health","grant_id":"3U01HG006379-12S3","title":"EHR-based Genomic Discovery and Implementation (Supplement)"},{"funder_name":"National Institutes of Health","grant_id":"1U01HG008701-01","title":"The Electronic Medical Records and Genomics (eMERGE) Network Phase III - 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