ArticleNPJ genomic medicine2022
Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis.
Article in NPJ genomic medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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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
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Sex-specific autosomal susceptibility loci in systemic sclerosis: a genome-wide association study.The Lancet. Rheumatology · 2026Pooled it
- Novel HLA class I and II insights into the pathogenesis of systemic sclerosis-associated interstitial lung disease.Annals of the rheumatic diseases · 2026Article
- Comprehensive Prediction Analysis of Novel Noncoding Regulatory Variants Identified in the MicroRNA Binding Regions in Complement System Genes.International journal of molecular sciences · 2026Article
- Distinct Effects of Complement C4A and C4B Copy Numbers in Systemic Sclerosis Serological and Clinical Subtypes.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Sex Bias in Systemic Sclerosis: from Clinical to Immunological Differences.Clinical reviews in allergy & immunology · 2025Review
- Improvement in long-term survival with mesenchymal stem cell transplantation in systemic sclerosis patients: a propensity score-matched cohort study.Stem cell research & therapy · 2025Article
- Sex differences in systemic sclerosis: from pathogenesis to clinical manifestations and treatment.Therapeutic advances in musculoskeletal disease · 2025Review
- Low C4A copy numbers and higher HERV gene insertion contributes to increased risk of SLE, with absence of association with disease phenotype and disease activity.Immunologic research · 2024Article
- Biomarkers in the Pathogenesis, Diagnosis, and Treatment of Systemic Sclerosis.Journal of inflammation research · 2023Review
Corrections and comments
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Authors and funding
25 authors at 20 institutions in 16 countries.
Funding
Abstract
Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals.
Identifiers
What OpenQuestion holds
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.