Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells

Author:

Lee Mark N.123,Ye Chun1,Villani Alexandra-Chloé12,Raj Towfique124,Li Weibo13,Eisenhaure Thomas M.13,Imboywa Selina H.2,Chipendo Portia I.2,Ran F. Ann15678,Slowikowski Kamil9,Ward Lucas D.110,Raddassi Khadir11,McCabe Cristin14,Lee Michelle H.2,Frohlich Irene Y.2,Hafler David A.8,Kellis Manolis110,Raychaudhuri Soumya121213,Zhang Feng678,Stranger Barbara E.1415,Benoist Christophe O.2,De Jager Philip L.124,Regev Aviv11617,Hacohen Nir123

Affiliation:

1. Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.

2. Harvard Medical School, Boston, MA 02115, USA.

3. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA.

4. Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115, USA.

5. Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

6. McGovern Institute for Brain Research, MIT, Cambridge, MA 02139, USA.

7. Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.

8. Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.

9. Bioinformatics and Integrative Genomics, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA.

10. Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA.

11. Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

12. Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

13. Arthritis Research UK Epidemiology Unit, Musculoskeletal Research Group, University of Manchester, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK.

14. Section of Genetic Medicine, The University of Chicago, Chicago, IL 60637, USA.

15. Institute for Genomics and Systems Biology, The University of Chicago, Chicago, IL 60637, USA.

16. Department of Biology, MIT, Cambridge, MA 02139, USA.

17. Howard Hughes Medical Institute.

Abstract

Immune Variation It is difficult to determine the mechanistic consequences of context-dependent genetic variants, some of which may be related to disease (see the Perspective by Gregersen ). Two studies now report on the effects of stimulating immunological monocytes and dendritic cells with proteins that can elicit a response to bacterial or viral infection and assess the functional links between genetic variants and profiles of gene expression. M. N. Lee et al. ( 10.1126/science.1246980 ) analyzed the expression of more than 400 genes, in dendritic cells from 534 healthy subjects, which revealed how expression quantitative trait loci (eQTLs) affect gene expression within the interferon-β and the Toll-like receptor 3 and 4 pathways. Fairfax et al. ( 10.1126/science.1246949 ) performed a genome-wide analysis to show that many eQTLs affected monocyte gene expression in a stimulus- or time-specific manner.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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