1. Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.
- Author
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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, and Bae SC
- Subjects
- Adult, Bayes Theorem, Case-Control Studies, China epidemiology, China ethnology, Asia, Eastern ethnology, Female, Genetic Predisposition to Disease epidemiology, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Japan epidemiology, Japan ethnology, Lupus Erythematosus, Systemic epidemiology, Male, Middle Aged, Prevalence, Republic of Korea epidemiology, Republic of Korea ethnology, Asian People genetics, Genetic Loci genetics, Genetic Predisposition to Disease ethnology, Lupus Erythematosus, Systemic ethnology, Lupus Erythematosus, Systemic genetics
- 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., 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., Results: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10
-8 ). 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 (rg =-0.242) and non-albumin protein (rg =0.238)., 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., Competing Interests: Competing interests: None declared., (© 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.)- Published
- 2021
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