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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00258

Exploring Impact of Rare Variation in Systemic Lupus Erythematosus by a Genome Wide Imputation Approach

  • 1Junta de Andalucía de Genómica e Investigación Oncológica (GENYO), Spain
  • 2Institute of Environmental Medicine, Karolinska Institutet, Sweden

The importance of low frequency and rare variation in complex disease genetics is difficult to estimate in patient populations. Genome-wide association studies are therefore, underpowered to detect rare variation. We have used a combined approach of genome-wide-based imputation with a highly stringent sequence kernel association (SKAT) test and a case-control burden test. We identified 98 candidate genes containing rare variation that in aggregate show association with SLE many of which have recognized immunological function, but also function and expression related to relevant tissues such as the joints, skin, blood or central nervous system. In addition we also find that there is a significant enrichment of genes annotated for disease-causing mutations in the OMIM database, suggesting that in complex diseases such as SLE, such mutations may be involved in subtle or combined phenotypes or could accelerate specific organ abnormalities found in the disease. We here provide an important resource of candidate genes for SLE.

Keywords: SLE, systemic lupus erythematosus, Imputated rare variation, GWAS - genome-wide association study, Sequence kernel association test, Aggregated case-control enrichment

Received: 27 Jul 2018; Accepted: 29 Jan 2019.

Edited by:

Laurence Morel, University of Florida, United States

Reviewed by:

Wentian Li, Feinstein Institute for Medical Research, United States
Jason Weinstein, Rutgers Biomedical and Health Sciences, United States
Celine Berthier, University of Michigan, United States  

Copyright: © 2019 Martinez-Bueno and Alarcón-Riquelme. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Manuel Martinez-Bueno, Junta de Andalucía de Genómica e Investigación Oncológica (GENYO), Granada, Spain, manuel.martinez@genyo.es