Genome-Wide Sequencing Identified Rare Genetic Variants for Childhood-Onset Monogenic Lupus
| العنوان: | Genome-Wide Sequencing Identified Rare Genetic Variants for Childhood-Onset Monogenic Lupus |
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| المؤلفون: | Melissa C. Misztal, Fangming Liao, Madeline Couse, Jingjing Cao, Daniela Dominguez, Lynette Lau, Christian R. Marshall, Sergey Naumenko, Andrea M. Knight, Deborah M. Levy, Linda T. Hiraki |
| المصدر: | The Journal of Rheumatology. 50:671-675 |
| بيانات النشر: | The Journal of Rheumatology, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Rheumatology, Immunology, Immunology and Allergy |
| الوصف: | ObjectiveGenetics play an important role in systemic lupus erythematosus (SLE) pathogenesis. We calculated the prevalence of rare variants in known monogenic lupus genes among children suspected of monogenic lupus.MethodsWe completed paired-end genome-wide sequencing (whole genome sequencing [WGS] or whole exome sequencing) in patients suspected of monogenic lupus, and focused on 36 monogenic lupus genes. We prioritized rare (minor allele frequency < 1%) exonic, nonsynonymous, and splice variants with predicted pathogenicity classified as deleterious variants (Combined Annotation Dependent Depletion [CADD], PolyPhen2, and Sorting Intolerant From Tolerant [SIFT] scores). Additional filtering restricted to predicted damaging variants by considering reported zygosity. In those with WGS (n = 69), we examined copy number variants (CNVs) > 1 kb in size. We created additive non-HLA and HLA SLE genetic risk scores (GRSs) using common SLE-risk single-nucleotide polymorphisms. We tested the relationship between SLE GRSs and the number of rare variants with multivariate logistic models, adjusted for sex, ancestry, and age of diagnosis.ResultsThe cohort included 71 patients, 80% female, with a mean age at diagnosis of 8.9 (SD 3.2) years. We identified predicted damaging variants in 9 (13%) patients who were significantly younger at diagnosis compared to those without a predicted damaging variant (6.8 [SD 2.1] years vs 9.2 [SD 3.2] years,P= 0.01). We did not identify damaging CNVs. There was no significant association between non-HLA or HLA SLE GRSs and the odds of carrying ≥ 1 rare variant in multivariate analyses.ConclusionIn a cohort of patients with suspected monogenic lupus who underwent genome-wide sequencing, 13% carried rare predicted damaging variants for monogenic lupus. Additional studies are needed to validate our findings. |
| تدمد: | 1499-2752 0315-162X |
| DOI: | 10.3899/jrheum.220513 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33f2bcd576f2aab226ee986c0d5d85de https://doi.org/10.3899/jrheum.220513 |
| رقم الانضمام: | edsair.doi.dedup.....33f2bcd576f2aab226ee986c0d5d85de |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14992752 0315162X |
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| DOI: | 10.3899/jrheum.220513 |