Journal article

Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles

Benjamin P Fairfax, Seiko Makino, Jayachandran Radhakrishnan, Katharine Plant, Stephen Leslie, Alexander Dilthey, Peter Ellis, Cordelia Langford, Fredrik O Vannberg, Julian C Knight



Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10(-15)), PRIC285 (P = 3.0 × 10(-10)) and an upstream region of CDKN1A (P = 2 × 10(-52)), suggesting roles for cell cycle regulation and peroxisome proliferator-acti..

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University of Melbourne Researchers


Awarded by Wellcome Trust

Awarded by European Research Council under the European Union

Awarded by National Institute for Health Research

Funding Acknowledgements

We are very grateful to all the volunteers who participated in this study, together with members of the Knight laboratory and A. Hill for their support. We thank A. Auton for his assistance in the identification of probes containing SNPs with European MAF of >0.01% using the 1000 Genomes Project data set and to J. Broxholme for bioinformatic support and mapping of all probes to the reference sequence. We thank G. Gibson, A. Hill and colleagues for critical reading of the manuscript and helpful suggestions. This work was supported by the Wellcome Trust (074318 to J. C. K., 088891 to B. P. F. and 075491/Z/04 to the core facilities at the Wellcome Trust Centre for Human Genetics), the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) (281824 to J. C. K.) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre.