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Article: Genome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus

TitleGenome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus
Authors
Keywordssystemic lupus erythematosus
GWAS
population genetics
complex diseases
autoimmune diseases
Issue Date2021
PublisherOxford University Press. The Journal's web site is located at http://rheumatology.oxfordjournals.org/
Citation
Rheumatology, 2021, Epub 2021-01-25, p. article no. keab016 How to Cite?
AbstractObjectives: To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility. Methods: A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analysed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry. A total of 26 774 individuals (9310 SLE cases and 17 464 controls) were included in this study. Results: Meta-analysis on four Chinese cohorts identifies KLF2 as a novel locus associated with SLE [rs2362475; odds ratio (OR) = 0.85, P=2.00E-09]. KLF2 is likely an Asian-specific locus as no evidence of association was detected in the four European cohorts (OR = 0.98, P =0.58), with evidence of heterogeneity (P=0.0019) between the two ancestral groups. Meta-analyses of results from both Chinese and Europeans identify STAB2 (rs10082873; OR= 0.89, P=4.08E-08) and DOT1L (rs4807205; OR= 1.12, P=8.17E-09) as trans-ancestral association loci, surpassing the genome-wide significance. Conclusions: We identified three loci associated with SLE, with KLF2 a likely Chinese-specific locus, highlighting the importance of studying diverse populations in SLE genetics. We hypothesize that DOT1L and KLF2 are plausible SLE treatment targets, with inhibitors of DOT1L and inducers of KLF2 already available clinically.
Persistent Identifierhttp://hdl.handle.net/10722/299735
ISSN
2020 Impact Factor: 7.58
2015 SCImago Journal Rankings: 1.449

 

DC FieldValueLanguage
dc.contributor.authorSong, Q-
dc.contributor.authorLEI, Y-
dc.contributor.authorShao, L-
dc.contributor.authorLi, W-
dc.contributor.authorKong, Q-
dc.contributor.authorLin, Z-
dc.contributor.authorQin, X-
dc.contributor.authorWei, W-
dc.contributor.authorHou, F-
dc.contributor.authorLi, J-
dc.contributor.authorGuo, X-
dc.contributor.authorMao, Y-
dc.contributor.authorCAO, Y-
dc.contributor.authorLIU, Z-
dc.contributor.authorZHENG, L-
dc.contributor.authorLIANG, R-
dc.contributor.authorJiang, Y-
dc.contributor.authorLiu, Y-
dc.contributor.authorZhang, L-
dc.contributor.authorYang, J-
dc.contributor.authorLau, YL-
dc.contributor.authorZhang, Y-
dc.contributor.authorBan, B-
dc.contributor.authorWang, YF-
dc.contributor.authorYang, W-
dc.date.accessioned2021-05-26T03:28:20Z-
dc.date.available2021-05-26T03:28:20Z-
dc.date.issued2021-
dc.identifier.citationRheumatology, 2021, Epub 2021-01-25, p. article no. keab016-
dc.identifier.issn1462-0324-
dc.identifier.urihttp://hdl.handle.net/10722/299735-
dc.description.abstractObjectives: To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility. Methods: A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analysed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry. A total of 26 774 individuals (9310 SLE cases and 17 464 controls) were included in this study. Results: Meta-analysis on four Chinese cohorts identifies KLF2 as a novel locus associated with SLE [rs2362475; odds ratio (OR) = 0.85, P=2.00E-09]. KLF2 is likely an Asian-specific locus as no evidence of association was detected in the four European cohorts (OR = 0.98, P =0.58), with evidence of heterogeneity (P=0.0019) between the two ancestral groups. Meta-analyses of results from both Chinese and Europeans identify STAB2 (rs10082873; OR= 0.89, P=4.08E-08) and DOT1L (rs4807205; OR= 1.12, P=8.17E-09) as trans-ancestral association loci, surpassing the genome-wide significance. Conclusions: We identified three loci associated with SLE, with KLF2 a likely Chinese-specific locus, highlighting the importance of studying diverse populations in SLE genetics. We hypothesize that DOT1L and KLF2 are plausible SLE treatment targets, with inhibitors of DOT1L and inducers of KLF2 already available clinically.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://rheumatology.oxfordjournals.org/-
dc.relation.ispartofRheumatology-
dc.rightsPost-print: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [insert journal title] following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: xxxxxxx [insert URL that the author will receive upon publication here].-
dc.subjectsystemic lupus erythematosus-
dc.subjectGWAS-
dc.subjectpopulation genetics-
dc.subjectcomplex diseases-
dc.subjectautoimmune diseases-
dc.titleGenome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus-
dc.typeArticle-
dc.identifier.emailYang, J: jingy09@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.emailWang, YF: yfwangbm@connect.hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.authorityLau, YL=rp00361-
dc.identifier.authorityYang, W=rp00524-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/rheumatology/keab016-
dc.identifier.pmid33493351-
dc.identifier.hkuros322556-
dc.identifier.volumeEpub 2021-01-25-
dc.identifier.spagearticle no. keab016-
dc.identifier.epagearticle no. keab016-
dc.publisher.placeUnited Kingdom-

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