Contributions of de novo variants to systemic lupus erythematosus.

Autor: Almlöf JC; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, 751 23, Uppsala, Sweden. jonas.carlsson@medsci.uu.se., Nystedt S; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, 751 23, Uppsala, Sweden., Mechtidou A; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, 751 23, Uppsala, Sweden., Leonard D; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, 751 85, Uppsala, Sweden., Eloranta ML; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, 751 85, Uppsala, Sweden., Grosso G; Department of Medicine, Karolinska Institutet, Rheumatology, Karolinska University Hospital, 171 77, Stockholm, Sweden., Sjöwall C; Department of Clinical and Experimental Medicine, Rheumatology/Division of Neuro and Inflammation Sciences, Linköping University, 581 83, Linköping, Sweden., Bengtsson AA; Department of Clinical Sciences, Rheumatology, Lund University, Skåne University Hospital, 222 42, Lund, Sweden., Jönsen A; Department of Clinical Sciences, Rheumatology, Lund University, Skåne University Hospital, 222 42, Lund, Sweden., Gunnarsson I; Department of Medicine, Karolinska Institutet, Rheumatology, Karolinska University Hospital, 171 77, Stockholm, Sweden., Svenungsson E; Department of Medicine, Karolinska Institutet, Rheumatology, Karolinska University Hospital, 171 77, Stockholm, Sweden., Rönnblom L; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, 751 85, Uppsala, Sweden., Sandling JK; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, 751 85, Uppsala, Sweden., Syvänen AC; Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, 751 23, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2021 Jan; Vol. 29 (1), pp. 184-193. Date of Electronic Publication: 2020 Jul 28.
DOI: 10.1038/s41431-020-0698-5
Abstrakt: 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.
Databáze: MEDLINE
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