Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression
While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) proj...
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| Published in | Cell Vol. 175; no. 6; pp. 1701 - 1715.e16 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
29.11.2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0092-8674 1097-4172 1097-4172 |
| DOI | 10.1016/j.cell.2018.10.022 |
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| Abstract | While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (https://dice-database.org).
[Display omitted]
•Cis-eQTLs for 12,254 unique genes were identified in 13 human immune cell types•41% of eGenes showed strong cis-association with genotype in a single cell type•GWAS variants were linked to cell types where their effects are most pronounced•Biological sex was associated with major differences in immune cell gene expression
Surveying gene expression and SNP genotypes across immune cell types from healthy humans reveals cis-eQTLs affecting over half of all expressed genes and demonstrates that variant effects often manifest in cell types other than those with highest gene expression. |
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| AbstractList | While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (https://dice-database.org).While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (https://dice-database.org). While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (Database of Immune Cell Expression, Expression quantitative trait loci (eQTLs) and Epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis -eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis -association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis ( http://dice-database.org ). In Brief: Surveying gene expression and SNP genotypes across immune cell types from healthy humans reveals cis-eQTLs affecting over half of all expressed genes and demonstrates that variant effects often manifest in cell types other than those with highest gene expression. While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (https://dice-database.org). While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (https://dice-database.org). [Display omitted] •Cis-eQTLs for 12,254 unique genes were identified in 13 human immune cell types•41% of eGenes showed strong cis-association with genotype in a single cell type•GWAS variants were linked to cell types where their effects are most pronounced•Biological sex was associated with major differences in immune cell gene expression Surveying gene expression and SNP genotypes across immune cell types from healthy humans reveals cis-eQTLs affecting over half of all expressed genes and demonstrates that variant effects often manifest in cell types other than those with highest gene expression. |
| Author | Valdovino-Gonzalez, Alan G. Vijayanand, Pandurangan Kronenberg, Mitchell Peters, Bjoern Rao, Anjana Zapardiel-Gonzalo, Jose Schmiedel, Benjamin J. Seumois, Grégory Madrigal, Ariel White, Brandie M. Singh, Divya Greenbaum, Jason A. Altay, Gokmen McVicker, Graham Ha, Brendan |
| AuthorAffiliation | 1 La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA 4 Department of Pharmacology and Moores Cancer Centre, University of California San Diego (UCSD), La Jolla, CA 92037, USA 7 University of Southampton, Faculty of Medicine, Southampton SO16 6YD, UK 2 Salk Institute for Biological Studies, La Jolla, CA 92037, USA 6 Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA 8 Lead contact 3 Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA 5 Division of Biological Sciences, University of California San Diego, La Jolla, CA 92037, USA |
| AuthorAffiliation_xml | – name: 7 University of Southampton, Faculty of Medicine, Southampton SO16 6YD, UK – name: 1 La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – name: 4 Department of Pharmacology and Moores Cancer Centre, University of California San Diego (UCSD), La Jolla, CA 92037, USA – name: 3 Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA – name: 6 Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA – name: 2 Salk Institute for Biological Studies, La Jolla, CA 92037, USA – name: 8 Lead contact – name: 5 Division of Biological Sciences, University of California San Diego, La Jolla, CA 92037, USA |
| Author_xml | – sequence: 1 givenname: Benjamin J. surname: Schmiedel fullname: Schmiedel, Benjamin J. organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 2 givenname: Divya surname: Singh fullname: Singh, Divya organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 3 givenname: Ariel surname: Madrigal fullname: Madrigal, Ariel organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 4 givenname: Alan G. surname: Valdovino-Gonzalez fullname: Valdovino-Gonzalez, Alan G. organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 5 givenname: Brandie M. surname: White fullname: White, Brandie M. organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 6 givenname: Jose surname: Zapardiel-Gonzalo fullname: Zapardiel-Gonzalo, Jose organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 7 givenname: Brendan surname: Ha fullname: Ha, Brendan organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 8 givenname: Gokmen surname: Altay fullname: Altay, Gokmen organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 9 givenname: Jason A. surname: Greenbaum fullname: Greenbaum, Jason A. organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 10 givenname: Graham surname: McVicker fullname: McVicker, Graham organization: Salk Institute for Biological Studies, La Jolla, CA 92037, USA – sequence: 11 givenname: Grégory surname: Seumois fullname: Seumois, Grégory organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 12 givenname: Anjana surname: Rao fullname: Rao, Anjana organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 13 givenname: Mitchell surname: Kronenberg fullname: Kronenberg, Mitchell organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 14 givenname: Bjoern surname: Peters fullname: Peters, Bjoern organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA – sequence: 15 givenname: Pandurangan surname: Vijayanand fullname: Vijayanand, Pandurangan email: vijay@lji.org organization: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30449622$$D View this record in MEDLINE/PubMed |
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| Title | Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression |
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