Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes

Author:

Raj Towfique1234,Rothamel Katie5,Mostafavi Sara6,Ye Chun4,Lee Mark N.34,Replogle Joseph M.14,Feng Ting5,Lee Michelle1,Asinovski Natasha5,Frohlich Irene1,Imboywa Selina1,Von Korff Alina1,Okada Yukinori23478,Patsopoulos Nikolaos A.1234,Davis Scott5,McCabe Cristin14,Paik Hyun-il5,Srivastava Gyan P.1234,Raychaudhuri Soumya2349,Hafler David A.410,Koller Daphne6,Regev Aviv411,Hacohen Nir412,Mathis Diane5,Benoist Christophe5,Stranger Barbara E.1314,De Jager Philip L.1234

Affiliation:

1. Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women’s Hospital, Boston, MA 02115, USA.

2. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

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

4. The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

5. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, MA 02115, USA.

6. Department of Computer Science, Stanford University, Stanford, CA 94305, USA.

7. Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

8. Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

9. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

10. Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.

11. Department of Biology, Massachusetts Institute of Technology, and Howard Hughes Medical Institute, Cambridge, MA 02139, USA.

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

13. Section of Genetic Medicine, Department of Medicine, University of Chicago, IL 60637, USA.

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

Abstract

Immunogenetic Variation Many genetic variants have been implicated in disease but their effects in function across tissues and cell-types remain to be resolved. Raj et al. (p. 519 ) present an analysis of expression quantative trait loci (eQTL) measuring messenger RNA levels and examined correlations between genotypes and gene expression in purified monocytes and T cells in healthy individuals of European, African, and Asian descent. Most, but not all, of the eQTLs and their effects on expression were shared between the populations, as well as a substantial proportion between the cell types. Links were found with disease-associated variants and loci that previous genome-wide analyses have implicated in neurodegenerative and autoimmune diseases.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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