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

AUTHORS

Raj TTowfique , Rothamel K Katie , Mostafavi S Sara , Ye C Chun , Lee MN Mark N , Replogle JM Joseph M , Feng T Ting , Lee M Michelle , Asinovski N Natasha , Frohlich I Irene , Imboywa S Selina , Von Korff A Alina , Okada Y Yukinori , Patsopoulos NA Nikolaos A , Davis S Scott , McCabe C Cristin , Paik HI Hyun-il , Srivastava GP Gyan P , Raychaudhuri S Soumya , Hafler DA David A , Koller D Daphne , Regev A Aviv , Hacohen N Nir , Mathis D Diane , Benoist C Christophe , Stranger BE Barbara E , De Jager PL Philip L . Science (New York, N.Y.). 2014 5 2; 344(6183). 519-23

PMID: 24786080[PubMed].

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.

The Ascano Laboratory