Contributions of de novo variants to systemic lupus erythematosus

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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.; Jönsen, Andreas; Gunnarsson, Iva; Svenungsson, Elisabet; Rönnblom, Lars; Sandling, Johanna K.; Syvänen, Ann Christine.

In: European Journal of Human Genetics, Vol. 29, No. 1, 2021, p. 184-193.

Research output: Contribution to journalArticle

Harvard

Almlöf, JC, Nystedt, S, Mechtidou, A, Leonard, D, Eloranta, ML, Grosso, G, Sjöwall, C, Bengtsson, AA, Jönsen, A, Gunnarsson, I, Svenungsson, E, Rönnblom, L, Sandling, JK & Syvänen, AC 2021, 'Contributions of de novo variants to systemic lupus erythematosus', European Journal of Human Genetics, vol. 29, no. 1, pp. 184-193. https://doi.org/10.1038/s41431-020-0698-5

APA

Almlöf, J. C., Nystedt, S., Mechtidou, A., Leonard, D., Eloranta, M. L., Grosso, G., Sjöwall, C., Bengtsson, A. A., Jönsen, A., Gunnarsson, I., Svenungsson, E., Rönnblom, L., Sandling, J. K., & Syvänen, A. C. (2021). Contributions of de novo variants to systemic lupus erythematosus. European Journal of Human Genetics, 29(1), 184-193. https://doi.org/10.1038/s41431-020-0698-5

CBE

Almlöf JC, Nystedt S, Mechtidou A, Leonard D, Eloranta ML, Grosso G, Sjöwall C, Bengtsson AA, Jönsen A, Gunnarsson I, Svenungsson E, Rönnblom L, Sandling JK, Syvänen AC. 2021. Contributions of de novo variants to systemic lupus erythematosus. European Journal of Human Genetics. 29(1):184-193. https://doi.org/10.1038/s41431-020-0698-5

MLA

Vancouver

Almlöf JC, Nystedt S, Mechtidou A, Leonard D, Eloranta ML, Grosso G et al. Contributions of de novo variants to systemic lupus erythematosus. European Journal of Human Genetics. 2021;29(1):184-193. https://doi.org/10.1038/s41431-020-0698-5

Author

Almlöf, Jonas Carlsson ; Nystedt, Sara ; Mechtidou, Aikaterini ; Leonard, Dag ; Eloranta, Maija Leena ; Grosso, Giorgia ; Sjöwall, Christopher ; Bengtsson, Anders A. ; Jönsen, Andreas ; Gunnarsson, Iva ; Svenungsson, Elisabet ; Rönnblom, Lars ; Sandling, Johanna K. ; Syvänen, Ann Christine. / Contributions of de novo variants to systemic lupus erythematosus. In: European Journal of Human Genetics. 2021 ; Vol. 29, No. 1. pp. 184-193.

RIS

TY - JOUR

T1 - Contributions of de novo variants to systemic lupus erythematosus

AU - Almlöf, Jonas Carlsson

AU - Nystedt, Sara

AU - Mechtidou, Aikaterini

AU - Leonard, Dag

AU - Eloranta, Maija Leena

AU - Grosso, Giorgia

AU - Sjöwall, Christopher

AU - Bengtsson, Anders A.

AU - Jönsen, Andreas

AU - Gunnarsson, Iva

AU - Svenungsson, Elisabet

AU - Rönnblom, Lars

AU - Sandling, Johanna K.

AU - Syvänen, Ann Christine

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41431-020-0698-5

DO - 10.1038/s41431-020-0698-5

M3 - Article

C2 - 32724065

AN - SCOPUS:85088698207

VL - 29

SP - 184

EP - 193

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1476-5438

IS - 1

ER -