title: Host genetic variation influences gene expression response to rhinovirus infection.
abstract: Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.
authors: Department of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
authors: Minal
authors: M
authors: Çalışkan
authors: Department of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
authors: Samuel W
authors: SW
authors: Baker
authors: Department of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
authors: Yoav
authors: Y
authors: Gilad
authors: Department of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
authors: Carole
authors: C
authors: Ober
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D003139:Common Cold / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: C431713:IRF5 protein, human; C056564:ITGA2B protein, human; D039421:Integrin alpha2; D050835:Interferon Regulatory Factors; C495139:MSR1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D051117:Scavenger Receptors, Class A; C483009:GSTM3 protein, human; D005982:Glutathione Transferase; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase