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Insights into rheumatic diseases from next-generation sequencing


Rheumatic diseases have complex aetiologies that are not fully understood, which makes the study of pathogenic mechanisms in these diseases a challenge for researchers. Next-generation sequencing (NGS) and related omics technologies, such as transcriptomics, epigenomics and genomics, provide an unprecedented genome-wide view of gene expression, environmentally responsive epigenetic changes and genetic variation. The integrated application of NGS technologies to samples from carefully phenotyped clinical cohorts of patients has the potential to solve remaining mysteries in the pathogenesis of several rheumatic diseases, to identify new therapeutic targets and to underpin a precision medicine approach to the diagnosis and treatment of rheumatic diseases. This Review provides an overview of the NGS technologies available, showcases important advances in rheumatic disease research already powered by these technologies and highlights NGS approaches that hold particular promise for generating new insights and advancing the field.

Key points

  • Next-generation sequencing (NGS) technologies have the potential to provide insight into the interaction between environmental factors and genetics in the pathogenesis of rheumatic diseases.

  • Transcriptomic studies have revealed disease-related pathways and novel pathogenic cell types in rheumatic diseases.

  • Epigenomic studies have revealed memory-related phenomena that might help to explain the chronicity of disease and have linked enhancers harbouring disease-associated allelic variants with target genes.

  • Whole-genome sequencing and exome sequencing have revealed causal mutations in rare Mendelian autoinflammatory diseases.

  • NGS approaches will substantially contribute to the application of precision medicine in rheumatology.

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Fig. 1: Overview of next-generation sequencing applications.
Fig. 2: Using transcriptomics to gain insight into rheumatic diseases and develop new therapeutics.
Fig. 3: Using epigenomics to gain insight into rheumatic diseases.
Fig. 4: Next-generation sequencing for precision medicine.


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The work of L.T.D., L.B.I. and K.-H.P.-M. was supported by grants from the US National Institutes of Health (NIH).

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Nature Reviews Rheumatology thanks P. Gaffney and the other anonymous reviewers for their contribution to the peer review of this work.

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All authors researched data for the article, provided substantial contributions to discussions of content and wrote the article. L.T.D., A.I. and L.B.I. reviewed and/or edited the manuscript before submission.

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Correspondence to Lionel B. Ivashkiv.

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R.M.S. declares that he is an employee of Novartis. The other authors declare no competing interests.

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Donlin, L.T., Park, SH., Giannopoulou, E. et al. Insights into rheumatic diseases from next-generation sequencing. Nat Rev Rheumatol 15, 327–339 (2019).

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