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Contributions of de novo variants to systemic lupus erythematosus

Almlöf, Jonas Carlsson ; Nystedt, Sara ; Mechtidou, Aikaterini ; Leonard, Dag ; Eloranta, Maija Leena ; Grosso, Giorgia ; Sjöwall, Christopher ; Bengtsson, Anders A. LU ; Jönsen, Andreas LU and Gunnarsson, Iva , et al. (2021) In European Journal of Human Genetics 29(1). p.184-193
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Human Genetics
volume
29
issue
1
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85088698207
  • pmid:32724065
ISSN
1018-4813
DOI
10.1038/s41431-020-0698-5
language
English
LU publication?
yes
id
f9130b1b-bd0c-444d-a1da-785fb71fe0cb
date added to LUP
2021-01-13 15:44:52
date last changed
2021-01-19 01:50:06
@article{f9130b1b-bd0c-444d-a1da-785fb71fe0cb,
  abstract     = {<p>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.</p>},
  author       = {Almlöf, Jonas Carlsson and Nystedt, Sara and Mechtidou, Aikaterini and Leonard, Dag and Eloranta, Maija Leena and Grosso, Giorgia and Sjöwall, Christopher and Bengtsson, Anders A. and Jönsen, Andreas and Gunnarsson, Iva and Svenungsson, Elisabet and Rönnblom, Lars and Sandling, Johanna K. and Syvänen, Ann Christine},
  issn         = {1018-4813},
  language     = {eng},
  number       = {1},
  pages        = {184--193},
  publisher    = {Nature Publishing Group},
  series       = {European Journal of Human Genetics},
  title        = {Contributions of de novo variants to systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1038/s41431-020-0698-5},
  doi          = {10.1038/s41431-020-0698-5},
  volume       = {29},
  year         = {2021},
}