ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Identification of Rare Variants in ATP8B4 as a Risk Factor for Systemic Sclerosis by Whole-Exome Sequencing.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 4 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 4 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Anti-RNA polymerase III antibodies in systemic sclerosis: prevalence and clinical associations from a systematic review and meta-analysis.Rheumatology (Oxford, England) · 2025Pooled it
- Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review.Frontiers in aging neuroscience · 2021Pooled it
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- Transethnic meta-analysis identifiesAnnals of the rheumatic diseases · 2017Pooled it
- Integrative exome sequencing and machine learning identify MICB and interferon pathway genes as contributors to SSc risk.Annals of the rheumatic diseases · 2025Article
- The impact of rare genetic variants on Alzheimer disease.Nature reviews. Neurology · 2025Review
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- Genomic Profiling for Predictive Treatment Strategies in Fibrotic Interstitial Lung Disease.Biomedicines · 2024Review
- High-throughput DNA sequence analysis elucidates novel insight into the genetic basis of adaptation in local sheep.Tropical animal health and production · 2024Article
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- The Ubiquitin Proteasome System and Skin Fibrosis.Molecular diagnosis & therapy · 2021Review
- Data mining of immune-related prognostic genes in metastatic melanoma microenvironment.Bioscience reports · 2020Article
- Genome-wide significant regions in 43 Utah high-risk families implicate multiple genes involved in risk for completed suicide.Molecular psychiatry · 2020Article
- Molecular "omic" signatures in systemic sclerosis.European journal of rheumatology · 2020Review
- The contribution of epigenetics to the pathogenesis and gender dimorphism of systemic sclerosis: a comprehensive overview.Therapeutic advances in musculoskeletal disease · 2020Review
- Genetic variants in Forkhead box O1 associated with predisposition to sepsis in a Chinese Han population.BMC infectious diseases · 2019Article
- Whole exome sequencing identifies hemizygous deletions in the UGT2B28 and USP17L2 genes in a three‑generation family with endometriosis.Molecular medicine reports · 2019Article
- Circular RNAs Hsa_circ_0002715 and Hsa_circ_0035197 in Peripheral Blood Are Novel Potential Biomarkers for New-Onset Rheumatoid Arthritis.Disease markers · 2019Article
- New insights into the genetics and epigenetics of systemic sclerosis.Nature reviews. Rheumatology · 2018Review
- Brief Report: Whole-Exome Sequencing to Identify Rare Variants and Gene Networks That Increase Susceptibility to Scleroderma in African Americans.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
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Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
objectiveTo determine the contribution of rare variants as genetic modifiers of the expressivity, penetrance, and severity of systemic sclerosis (SSc).
methodsWe performed whole-exome sequencing of 78 European American patients with SSc, including 35 patients without pulmonary arterial hypertension (PAH) and 43 patients with PAH. Association testing of case-control probability for rare variants was performed using the unified sequence kernel association test with optimal kernel weighting and small sample adjustment by comparing all SSc patients with a reference population of 3,179 controls from the Exome Sequencing Project 5,500 exome data set. Replication genotyping was performed in an independent sample of 3,263 patients (415 patients with SSc and 2,848 controls). We conducted expression profiling of messenger RNA from 61 SSc patients (19 without PAH and 42 with PAH) and 41 corresponding controls.
resultsThe ATP8B4 gene was associated with a significant increase in the risk of SSc (P = 2.77 × 10(-7)). Among the 64 ATP8B4 variants tested, a single missense variant, c.1308C>G (F436L, rs55687265), provided the most compelling evidence of association (P = 9.35 × 10(-10), odds ratio [OR] 6.11), which was confirmed in the replication cohort (P = 0.012, OR 1.86) and meta-analysis (P = 1.92 × 10(-7), OR 2.5). Genes involved in E3 ubiquitin-protein ligase complex (ASB10) and cyclic nucleotide gated channelopathies (CNGB3) as well as HLA-DRB5 and HSPB2 (heat-shock protein 27) provided additional evidence of association (P < 10(-5)). Differential ATP8B4 expression was observed among the SSc patients compared to the controls (P = 0.0005).
conclusionATP8B4 may represent a putative genetic risk factor for SSc and pulmonary vascular complications.
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