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Posts Tagged ‘Autoimmune and Neurodegenerative Risk Alleles in Leukocytes’

BWH Researchers: Genetic Variations can Influence Immune Cell Function: Risk Factors for Alzheimer’s Disease,DM, and MS later in life

 

Reporter: Aviva Lev-Ari, PhD, RN

 

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

  1. Towfique Raj1,2,3,4,
  2. Katie Rothamel5,
  3. Sara Mostafavi6,
  4. Chun Ye4,
  5. Mark N. Lee3,4,
  6. Joseph M. Replogle1,4,
  7. Ting Feng5,
  8. Michelle Lee1,
  9. Natasha Asinovski5,
  10. Irene Frohlich1,
  11. Selina Imboywa1,
  12. Alina Von Korff1,
  13. Yukinori Okada2,3,4,7,8,
  14. Nikolaos A. Patsopoulos1,2,3,4,
  15. Scott Davis5,
  16. Cristin McCabe1,4,
  17. Hyun-il Paik5,
  18. Gyan P. Srivastava1,2,3,4,
  19. Soumya Raychaudhuri2,3,4,9,
  20. David A. Hafler4,10,
  21. Daphne Koller6,
  22. Aviv Regev4,11,
  23. Nir Hacohen4,12,
  24. Diane Mathis5,
  25. Christophe Benoist5,*,
  26. Barbara E. Stranger13,14,*,
  27. Philip L. De Jager1,2,3,4,*

+Author Affiliations


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

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

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

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

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

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

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

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

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

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

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

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

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

  14. 14Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA.
  1. *Corresponding author. E-mail: christophe_benoist@hms.harvard.edu (C.B.);bstranger@medicine.bsd.uchicago.edu (B.E.S.); pdejager@partners.org (P.L.D.J.)


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.

ABSTRACT

To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4+ T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell–specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer’s and Parkinson’s disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.

SOURCE

http://www.sciencemag.org/content/344/6183/519.abstract?elq=3d8c1a6f41594f318278412bc0df79a2&elqCampaignId=14

 

 

 

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