Universität zu Köln

Kerick, Martin ORCID: 0000-0002-6298-4514, Acosta-Herrera, Marialbert ORCID: 0000-0002-9868-6535, Pilar Simeon-Aznar, Carmen, Luis Callejas, Jose, Assassi, Shervin, Proudman, Susanna M., Nikpour, Mandana, Hunzelmann, Nicolas, Moroncini, Gianluca, de Vries-Bouwstra, Jeska K., Orozco, Gisela, Barton, Anne, Herrick, Ariane L., Terao, Chikashi, Allanore, Yannick, Fonseca, Carmen, Eugenia Alarcon-Riquelme, Marta, Radstake, Timothy R. D. J., Beretta, Lorenzo, Denton, Christopher P., Mayes, Maureen D. and Martin, Javier (2022). Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis. npj Genom. Med., 7 (1). BERLIN: NATURE PORTFOLIO. ISSN 2056-7944

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kerick, Martin UNSPECIFIED orcid.org/0000-0002-6298-4514 UNSPECIFIED Acosta-Herrera, Marialbert UNSPECIFIED orcid.org/0000-0002-9868-6535 UNSPECIFIED Pilar Simeon-Aznar, Carmen UNSPECIFIED UNSPECIFIED UNSPECIFIED Luis Callejas, Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Assassi, Shervin UNSPECIFIED UNSPECIFIED UNSPECIFIED Proudman, Susanna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nikpour, Mandana UNSPECIFIED UNSPECIFIED UNSPECIFIED Hunzelmann, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED Moroncini, Gianluca UNSPECIFIED UNSPECIFIED UNSPECIFIED de Vries-Bouwstra, Jeska K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Orozco, Gisela UNSPECIFIED UNSPECIFIED UNSPECIFIED Barton, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrick, Ariane L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Terao, Chikashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Allanore, Yannick UNSPECIFIED UNSPECIFIED UNSPECIFIED Fonseca, Carmen UNSPECIFIED UNSPECIFIED UNSPECIFIED Eugenia Alarcon-Riquelme, Marta UNSPECIFIED UNSPECIFIED UNSPECIFIED Radstake, Timothy R. D. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beretta, Lorenzo UNSPECIFIED UNSPECIFIED UNSPECIFIED Denton, Christopher P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mayes, Maureen D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Javier UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-697143
DOI:	10.1038/s41525-022-00327-8
Journal or Publication Title:	npj Genom. Med.
Volume:	7
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2056-7944
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COPY-NUMBER VARIATION; RP-C4-CYP21-TNX RCCX MODULES; VARIANTS; DISEASE; SUSCEPTIBILITY; HEALTH; RISK; CLASSIFICATION; AUTOIMMUNITY; RECEPTORS Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69714