Approaches and advances in the genetic causes of autoimmune disease and their implications


Genome-wide association studies are transformative in revealing the polygenetic basis of common diseases, with autoimmune diseases leading the charge. Although the field is just over 10 years old, advances in understanding the underlying mechanistic pathways of these conditions, which result from a dense multifactorial blend of genetic, developmental and environmental factors, have already been informative, including insights into therapeutic possibilities. Nevertheless, the challenge of identifying the actual causal genes and pathways and their biological effects on altering disease risk remains for many identified susceptibility regions. It is this fundamental knowledge that will underpin the revolution in patient stratification, the discovery of therapeutic targets and clinical trial design in the next 20 years. Here we outline recent advances in analytical and phenotyping approaches and the emergence of large cohorts with standardized gene-expression data and other phenotypic data that are fueling a bounty of discovery and improved understanding of human physiology.

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Fig. 1: Refining complex disease associations in different cellular activation states via chromatin annotation and chromatin-conformation capture.

Change history

  • 15 April 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • 07 February 2019

    In the version of this article initially published, the bibliographic information for reference 2 was incorrect in the reference list, and reference 2 was cited incorrectly at the end of the second sentence in the second paragraph (“...were identified2.”). The correct reference 2 is as follows: “Kong, A. et al. The nature of nurture: Effects of parental genotypes. Science 359, 424–428 (2018).” The reference that should be cited at the end of the aforementioned sentence, which should be numbered ‘5’ (“...were identified5.”), is as follows: “Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376–381 (2014).” All subsequent references (5–161) should be renumbered accordingly (6–162) in the list and text. Also, several of the gene symbols in Table 2 were formatted incorrectly (without commas); the correct gene symbols are as follows: column 3 row 13, RBM17, IL2RA; column 3 row 30, DEXI, CLEC16A; column 3 row 39, UBASH3A, ICOSLG; column 4 row 15, PTEN, KLLN; column 4 row 21, CLEC7A, CLEC9A; and column 5 rows 7–9, AL391559.1, ENSG00000238747, RP11-63K6.7, RP3-512E2.2. The errors have been corrected in the HTML and PDF version of the article.


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We thank the JDRF (grant codes 9-2011-253 and 5-SRA-2015-130-A-N) and Wellcome (grant codes 091157 and 107212). O.S.B. is funded by Wellcome (grant code WT107881).

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Inshaw, J.R.J., Cutler, A.J., Burren, O.S. et al. Approaches and advances in the genetic causes of autoimmune disease and their implications. Nat Immunol 19, 674–684 (2018).

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