An immunochip-based interrogation of scleroderma susceptibility variants identifies a novel association at DNASE1L3

Zochling, Jane, Newell, Felicity, Charlesworth, Jac C., Leo, Paul, Stankovich, Jim, Cortes, Adrian, Zhou, Yuan, Stevens, Wendy, Sahhar, Joanne, Roddy, Janet, Nash, Peter, Tymms, Kathleen, Rischmueller, Maureen, Lester, Sue, Proudman, Susanna and Brown, Matthew A. (2014) An immunochip-based interrogation of scleroderma susceptibility variants identifies a novel association at DNASE1L3. Arthritis Research & Therapy, 16 5: 1-7. doi:10.1186/s13075-014-0438-8

Author Zochling, Jane
Newell, Felicity
Charlesworth, Jac C.
Leo, Paul
Stankovich, Jim
Cortes, Adrian
Zhou, Yuan
Stevens, Wendy
Sahhar, Joanne
Roddy, Janet
Nash, Peter
Tymms, Kathleen
Rischmueller, Maureen
Lester, Sue
Proudman, Susanna
Brown, Matthew A.
Title An immunochip-based interrogation of scleroderma susceptibility variants identifies a novel association at DNASE1L3
Journal name Arthritis Research & Therapy   Check publisher's open access policy
ISSN 1478-6354
Publication date 2014-01
Year available 2014
Sub-type Article (original research)
DOI 10.1186/s13075-014-0438-8
Open Access Status DOI
Volume 16
Issue 5
Start page 1
End page 7
Total pages 7
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2015
Language eng
Formatted abstract

The aim of the study was to interrogate the genetic architecture and autoimmune pleiotropy of scleroderma susceptibility in the Australian population.


We genotyped individuals from a well-characterized cohort of Australian scleroderma patients with the Immunochip, a custom array enriched for single nucleotide polymorphisms (SNPs) at immune loci. Controls were taken from the 1958 British Birth Cohort. After data cleaning and adjusting for population stratification the final dataset consisted of 486 cases, 4,458 controls and 146,525 SNPs. Association analyses were conducted using logistic regression in PLINK. A replication study was performed using 833 cases and 1,938 controls.


A total of eight loci with suggestive association (P <10-4.5) were identified, of which five showed significant association in the replication cohort (HLA-DRB1, DNASE1L3, STAT4, TNP03-IRF5 and VCAM1). The most notable findings were at the DNASE1L3 locus, previously associated with systemic lupus erythematosus, and VCAM1, a locus not previously associated with human disease. This study identified a likely functional variant influencing scleroderma susceptibility at the DNASE1L3 locus; a missense polymorphism rs35677470 in DNASE1L3, with an odds ratio of 2.35 (P = 2.3?×?10?10) in anti-centromere antibody (ACA) positive cases.


This pilot study has confirmed previously reported scleroderma associations, revealed further genetic overlap between scleroderma and systemic lupus erythematosus, and identified a putative novel scleroderma susceptibility locus.
Keyword Systemic lupus erythematosus
Genome wide association
Single nucleotide polymorphisms
Classical HLA alleles
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
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Created: Wed, 18 Mar 2015, 15:29:37 EST by Kylie Hengst on behalf of UQ Diamantina Institute