Kerick, Martin;
Acosta-Herrera, Marialbert;
Pilar Simeon-Aznar, Carmen;
Luis Callejas, Jose;
Assassi, Shervin;
Proudman, Susanna M;
Nikpour, Mandana;
... Martin, Javier; + view all
(2022)
Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis.
npj Genomic Medicine
, 7
, Article 57. 10.1038/s41525-022-00327-8.
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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.
| Type: | Article |
|---|---|
| Title: | Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41525-022-00327-8 |
| Publisher version: | https://doi.org/10.1038/s41525-022-00327-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, COPY-NUMBER VARIATION, RP-C4-CYP21-TNX RCCX MODULES, VARIANTS, DISEASE, SUSCEPTIBILITY, HEALTH, RISK, CLASSIFICATION, AUTOIMMUNITY, RECEPTORS |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10157681 |
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