Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes

Science. 2014 May 2;344(6183):519-23. doi: 10.1126/science.1249547.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / genetics
  • Alleles
  • Alzheimer Disease / ethnology
  • Alzheimer Disease / genetics
  • Autoimmune Diseases / ethnology
  • Autoimmune Diseases / genetics*
  • Autoimmunity / genetics*
  • CD4-Positive T-Lymphocytes / immunology*
  • Ethnicity / genetics
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Humans
  • Immunity, Innate / genetics
  • Monocytes / immunology*
  • Multiple Sclerosis / ethnology
  • Multiple Sclerosis / genetics
  • Neurodegenerative Diseases / ethnology
  • Neurodegenerative Diseases / genetics*
  • Parkinson Disease / ethnology
  • Parkinson Disease / genetics
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Rheumatic Fever / ethnology
  • Rheumatic Fever / genetics
  • Transcriptome

Associated data

  • GEO/GSE56035