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

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissionsoup.com..

OBJECTIVES: 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:60

Enthalten in:

Rheumatology (Oxford, England) - 60(2021), 9 vom: 01. Sept., Seite 4407-4417

Sprache:

Englisch

Beteiligte Personen:

Song, Qin [VerfasserIn]
Lei, Yao [VerfasserIn]
Shao, Li [VerfasserIn]
Li, Weiyang [VerfasserIn]
Kong, Qingsheng [VerfasserIn]
Lin, Zhiming [VerfasserIn]
Qin, Xiao [VerfasserIn]
Wei, Wei [VerfasserIn]
Hou, Fei [VerfasserIn]
Li, Jian [VerfasserIn]
Guo, Xianghua [VerfasserIn]
Mao, Yujing [VerfasserIn]
Cao, Yujie [VerfasserIn]
Liu, Zhongyi [VerfasserIn]
Zheng, Lichuan [VerfasserIn]
Liang, Rui [VerfasserIn]
Jiang, Yuping [VerfasserIn]
Liu, Yan [VerfasserIn]
Zhang, Lili [VerfasserIn]
Yang, Jing [VerfasserIn]
Lau, Yu Lung [VerfasserIn]
Zhang, Yan [VerfasserIn]
Ban, Bo [VerfasserIn]
Wang, Yong-Fei [VerfasserIn]
Yang, Wanling [VerfasserIn]

Links:

Volltext

Themen:

Autoimmune diseases
Cell Adhesion Molecules, Neuronal
Complex diseases
DOT1L protein, human
EC 2.1.1.-
EC 2.1.1.43
GWAS
Histone-Lysine N-Methyltransferase
Journal Article
KLF2 protein, human
Kruppel-Like Transcription Factors
Population genetics
Research Support, Non-U.S. Gov't
STAB2 protein, human
Systemic lupus erythematosus

Anmerkungen:

Date Completed 04.10.2021

Date Revised 04.10.2021

published: Print

Citation Status MEDLINE

doi:

10.1093/rheumatology/keab016

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM320553965