ArticleHuman molecular genetics2018
De novo mutations implicate novel genes in systemic lupus erythematosus.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pooled it
- Is clonal haematopoiesis the missing link between lupus and cardiovascular disease?Rheumatology (Oxford, England) · 2026Review
- Systematic dysregulation of immune-related alternative polyadenylation in systemic lupus erythematosus contributes to patient stratification.Journal of translational autoimmunity · 2026Article
- Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus.Frontiers in genetics · 2024Review
- CTRP4/interleukin-6 receptor signaling ameliorates autoimmune encephalomyelitis by suppressing Th17 cell differentiation.The Journal of clinical investigation · 2023Article
- Genes and Microbiota Interaction in Monogenic Autoimmune Disorders.Biomedicines · 2023Review
- Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.Human genomics · 2023Article
- COVID-19 severity: does the genetic landscape of rare variants matter?Frontiers in genetics · 2023Article
- Childhood-onset systemic lupus erythematosus: characteristics and the prospect of glucocorticoid pulse therapy.Frontiers in immunology · 2023Review
- Systemic lupus erythematosus as a genetic disease.Clinical immunology (Orlando, Fla.) · 2022Article
- CTRP4 ablation impairs associative learning and memory.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Effects of targeting the transcription factors Ikaros and Aiolos on B cell activation and differentiation in systemic lupus erythematosus.Lupus science & medicine · 2021Article
- Article
- Contributions of de novo variants to systemic lupus erythematosus.European journal of human genetics : EJHG · 2021Article
- Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing.Annals of the rheumatic diseases · 2021Article
- Loss of CTRP4 alters adiposity and food intake behaviors in obese mice.American journal of physiology. Endocrinology and metabolism · 2020Article
- 'There and Back Again'-Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension.Genes · 2020Review
- New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond.Journal of clinical medicine · 2020Review
- Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus.Human genetics · 2019Article
- Systematic Review of Gut Microbiota and Major Depression.Frontiers in psychiatry · 2019Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The omnigenic model of complex disease stipulates that the majority of the heritability will be explained by the effects of common variation on genes in the periphery of core disease pathways. Rare variant associations, expected to explain far less of the heritability, may be enriched in core disease genes and thus will be instrumental in the understanding of complex disease pathogenesis and their potential therapeutic targets. Here, using complementary whole-exome sequencing, high-density imputation, and in vitro cellular assays, we identify candidate core genes in the pathogenesis of systemic lupus erythematosus (SLE). Using extreme-phenotype sampling, we sequenced the exomes of 30 SLE parent-affected-offspring trios and identified 14 genes with missense de novo mutations (DNM), none of which are within the >80 SLE susceptibility loci implicated through genome-wide association studies. In a follow-up cohort of 10, 995 individuals of matched European ancestry, we imputed genotype data to the density of the combined UK10K-1000 genomes Phase III reference panel across the 14 candidate genes. Gene-level analyses indicate three functional candidates: DNMT3A, PRKCD, and C1QTNF4. We identify a burden of rare variants across PRKCD associated with SLE risk (P = 0.0028), and across DNMT3A associated with two severe disease prognosis sub-phenotypes (P = 0.0005 and P = 0.0033). We further characterise the TNF-dependent functions of the third candidate gene C1QTNF4 on NF-κB activation and apoptosis, which are inhibited by the p.His198Gln DNM. Our results identify three novel genes in SLE susceptibility and support extreme-phenotype sampling and DNM gene discovery to aid the search for core disease genes implicated through rare variation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.