Contributions of de novo variants to systemic lupus erythematosus

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By performing whole-genome sequencing in a Swedish cohort of 71 parent-offspring trios, in which the child in each family is affected by systemic lupus erythematosus (SLE, OMIM 152700), we investigated the contribution of de novo variants to risk of SLE. We found de novo single nucleotide variants (SNVs) to be significantly enriched in gene promoters in SLE patients compared with healthy controls at a level corresponding to 26 de novo promoter SNVs more in each patient than expected. We identified 12 de novo SNVs in promoter regions of genes that have been previously implicated in SLE, or that have functions that could be of relevance to SLE. Furthermore, we detected three missense de novo SNVs, five de novo insertion-deletions, and three de novo structural variants with potential to affect the expression of genes that are relevant for SLE. Based on enrichment analysis, disease-affecting de novo SNVs are expected to occur in one-third of SLE patients. This study shows that de novo variants in promoters commonly contribute to the genetic risk of SLE. The fact that de novo SNVs in SLE were enriched to promoter regions highlights the importance of using whole-genome sequencing for identification of de novo variants.


  • Jonas Carlsson Almlöf
  • Sara Nystedt
  • Aikaterini Mechtidou
  • Dag Leonard
  • Maija Leena Eloranta
  • Giorgia Grosso
  • Christopher Sjöwall
  • Anders A. Bengtsson
  • Andreas Jönsen
  • Iva Gunnarsson
  • Elisabet Svenungsson
  • Lars Rönnblom
  • Johanna K. Sandling
  • Ann Christine Syvänen
Enheter & grupper
Externa organisationer
  • Uppsala universitet
  • Karolinska University Hospital
  • Linköping University

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
Sidor (från-till)184-193
Antal sidor10
TidskriftEuropean Journal of Human Genetics
Utgåva nummer1
StatusPublished - 2021
Peer review utfördJa