Back to Search Start Over

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

Authors :
Yin X
Kim K
Suetsugu H
Bang SY
Wen L
Koido M
Ha E
Liu L
Sakamoto Y
Jo S
Leng RX
Otomo N
Laurynenka V
Kwon YC
Sheng Y
Sugano N
Hwang MY
Li W
Mukai M
Yoon K
Cai M
Ishigaki K
Chung WT
Huang H
Takahashi D
Lee SS
Wang M
Karino K
Shim SC
Zheng X
Miyamura T
Kang YM
Ye D
Nakamura J
Suh CH
Tang Y
Motomura G
Park YB
Ding H
Kuroda T
Choe JY
Li C
Niiro H
Park Y
Shen C
Miyamoto T
Ahn GY
Fei W
Takeuchi T
Shin JM
Li K
Kawaguchi Y
Lee YK
Wang Y
Amano K
Park DJ
Yang W
Tada Y
Yamaji K
Shimizu M
Atsumi T
Suzuki A
Sumida T
Okada Y
Matsuda K
Matsuo K
Kochi Y
Kottyan LC
Weirauch MT
Parameswaran S
Eswar S
Salim H
Chen X
Yamamoto K
Harley JB
Ohmura K
Kim TH
Yang S
Yamamoto T
Kim BJ
Shen N
Ikegawa S
Lee HS
Zhang X
Terao C
Cui Y
Bae SC
Source :
Annals of the rheumatic diseases [Ann Rheum Dis] 2021 May; Vol. 80 (5), pp. 632-640. Date of Electronic Publication: 2020 Dec 03.
Publication Year :
2021

Abstract

Objective: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.<br />Methods: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.<br />Results: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10 <superscript>-8</superscript> ). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r <subscript>g</subscript> =-0.242) and non-albumin protein (r <subscript>g</subscript> =0.238).<br />Conclusion: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Details

Language :
English
ISSN :
1468-2060
Volume :
80
Issue :
5
Database :
MEDLINE
Journal :
Annals of the rheumatic diseases
Publication Type :
Academic Journal
Accession number :
33272962
Full Text :
https://doi.org/10.1136/annrheumdis-2020-219209