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

TitleMeta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
Authors
Keywordsepidemiology
genetic
lupus erythematosus
polymorphism
systemic
Issue Date2020
PublisherBMJ Publishing Group. The Journal's web site is located at http://ard.bmjjournals.com/
Citation
Annals of the Rheumatic Diseases, 2020, v. 80 n. 5, p. 632-640 How to Cite?
AbstractObjective 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.
Persistent Identifierhttp://hdl.handle.net/10722/295335
ISSN
2020 Impact Factor: 19.103
2020 SCImago Journal Rankings: 6.333
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYin, X-
dc.contributor.authorKim, K-
dc.contributor.authorSuetsugu, H-
dc.contributor.authorBang, SY-
dc.contributor.authorWen, L-
dc.contributor.authorKoido, M-
dc.contributor.authorHa, E-
dc.contributor.authorLiu, L-
dc.contributor.authorSakamoto, Y-
dc.contributor.authorJo, S-
dc.contributor.authorLeng, RX-
dc.contributor.authorOtomo, N-
dc.contributor.authorLaurynenka, V-
dc.contributor.authorKwon, YC-
dc.contributor.authorSheng, Y-
dc.contributor.authorSugano, N-
dc.contributor.authorHwang, MY-
dc.contributor.authorLi, W-
dc.contributor.authorMukai, M-
dc.contributor.authorYoon, K-
dc.contributor.authorCai, M-
dc.contributor.authorIshigaki, K-
dc.contributor.authorChung, WT-
dc.contributor.authorHuang, H-
dc.contributor.authorTakahashi, D-
dc.contributor.authorLee, SS-
dc.contributor.authorWang, M-
dc.contributor.authorKarino, K-
dc.contributor.authorShim, SC-
dc.contributor.authorZheng, X-
dc.contributor.authorMiyamura, T-
dc.contributor.authorKang, YM-
dc.contributor.authorYe, D-
dc.contributor.authorNakamura, J-
dc.contributor.authorSuh, CH-
dc.contributor.authorTang, Y-
dc.contributor.authorMotomura, G-
dc.contributor.authorPark, YB-
dc.contributor.authorDing, H-
dc.contributor.authorKuroda, T-
dc.contributor.authorChoe, JY-
dc.contributor.authorLi, C-
dc.contributor.authorNiiro, H-
dc.contributor.authorPark, Y-
dc.contributor.authorShen, C-
dc.contributor.authorMiyamoto, T-
dc.contributor.authorAhn, GY-
dc.contributor.authorFei, W-
dc.contributor.authorTakeuchi, T-
dc.contributor.authorShin, JM-
dc.contributor.authorLi, K-
dc.contributor.authorKawaguchi, Y-
dc.contributor.authorLee, YK-
dc.contributor.authorWang, Y-
dc.contributor.authorAmano, K-
dc.contributor.authorPark, DJ-
dc.contributor.authorYang, W-
dc.contributor.authorTada, Y-
dc.contributor.authorYamaji, K-
dc.contributor.authorShimizu, M-
dc.contributor.authorAtsumi, T-
dc.contributor.authorSuzuki, A-
dc.contributor.authorSumida, T-
dc.contributor.authorOkada, Y-
dc.contributor.authorMatsuda, K-
dc.contributor.authorMatsuo, K-
dc.contributor.authorKochi, Y-
dc.contributor.authorKottyan, LC-
dc.contributor.authorWeirauch, MT-
dc.contributor.authorParameswaran, S-
dc.contributor.authorEswar, S-
dc.contributor.authorSalim, H-
dc.contributor.authorChen, X-
dc.contributor.authorYamamoto, K-
dc.contributor.authorHarley, JB-
dc.contributor.authorOhmura, K-
dc.contributor.authorKim, TH-
dc.contributor.authorYang, S-
dc.contributor.authorYamamoto, T-
dc.contributor.authorKim, BJ-
dc.contributor.authorShen, N-
dc.contributor.authorIkegawa, S-
dc.contributor.authorLee, HS-
dc.contributor.authorZhang, X-
dc.contributor.authorTerao, C-
dc.contributor.authorCui, Y-
dc.contributor.authorBae, SC-
dc.date.accessioned2021-01-11T13:58:39Z-
dc.date.available2021-01-11T13:58:39Z-
dc.date.issued2020-
dc.identifier.citationAnnals of the Rheumatic Diseases, 2020, v. 80 n. 5, p. 632-640-
dc.identifier.issn0003-4967-
dc.identifier.urihttp://hdl.handle.net/10722/295335-
dc.description.abstractObjective 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.-
dc.languageeng-
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://ard.bmjjournals.com/-
dc.relation.ispartofAnnals of the Rheumatic Diseases-
dc.rightsAnnals of the Rheumatic Diseases. Copyright © BMJ Publishing Group.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectepidemiology-
dc.subjectgenetic-
dc.subjectlupus erythematosus-
dc.subjectpolymorphism-
dc.subjectsystemic-
dc.titleMeta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus-
dc.typeArticle-
dc.identifier.emailWang, Y: yfwangbm@connect.hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.authorityYang, W=rp00524-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/annrheumdis-2020-219209-
dc.identifier.pmid33272962-
dc.identifier.pmcidPMC8053352-
dc.identifier.scopuseid_2-s2.0-85097241195-
dc.identifier.hkuros320874-
dc.identifier.volume80-
dc.identifier.issue5-
dc.identifier.spage632-
dc.identifier.epage640-
dc.identifier.isiWOS:000641486900036-
dc.publisher.placeUnited Kingdom-

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