Article: Genome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in Asian populations

TitleGenome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in Asian populations
Authors
Issue Date2015
PublisherBMJ Publishing Group. The Journal's web site is located at http://ard.bmjjournals.com/
Citation
Annals of the Rheumatic Diseases, How to Cite?
AbstractOBJECTIVES: Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility. METHODS: The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction. RESULTS: Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets. CONCLUSIONS: Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.
Persistent Identifierhttp://hdl.handle.net/10722/211803
ISSN
2015 Impact Factor: 12.384
2015 SCImago Journal Rankings: 4.537

 

DC FieldValueLanguage
dc.contributor.authorZhang, Y-
dc.contributor.authorYang, J-
dc.contributor.authorZhang, J-
dc.contributor.authorSun, L-
dc.contributor.authorHirankarn, N-
dc.contributor.authorPan, HF-
dc.contributor.authorLau, WCS-
dc.contributor.authorChan, DTM-
dc.contributor.authorLee, TL-
dc.contributor.authorLeung, AMH-
dc.contributor.authorMok, CC-
dc.contributor.authorZhang, L-
dc.contributor.authorWang, Y-
dc.contributor.authorShen, JJ-
dc.contributor.authorWong, SN-
dc.contributor.authorLee, KW-
dc.contributor.authorHo, MHK-
dc.contributor.authorLee, PPW-
dc.contributor.authorChung, BHY-
dc.contributor.authorChong, CY-
dc.contributor.authorWong, RWS-
dc.contributor.authorMok, TMY-
dc.contributor.authorWong, WHS-
dc.contributor.authorTong, KL-
dc.contributor.authorTse, NKC-
dc.contributor.authorLi, XP-
dc.contributor.authorAvihingsanon, Y-
dc.contributor.authorRianthavorn, P-
dc.contributor.authorDeekajorndej, T-
dc.contributor.authorSuphapeetiporn, K-
dc.contributor.authorShotelersuk, V-
dc.contributor.authorYing, SKY-
dc.contributor.authorFung, SKS-
dc.contributor.authorLai, WM-
dc.contributor.authorWong, CM-
dc.contributor.authorNg, IOL-
dc.contributor.authorGarcia-Barcelo, MM-
dc.contributor.authorCherny, SS-
dc.contributor.authorCui, Y-
dc.contributor.authorSham, PC-
dc.contributor.authorYang, S-
dc.contributor.authorYe, DQ-
dc.contributor.authorZhang, XJ-
dc.contributor.authorLau, YL-
dc.contributor.authorYang, W-
dc.date.accessioned2015-07-21T02:11:13Z-
dc.date.available2015-07-21T02:11:13Z-
dc.date.issued2015-
dc.identifier.citationAnnals of the Rheumatic Diseases,-
dc.identifier.issn0003-4967-
dc.identifier.urihttp://hdl.handle.net/10722/211803-
dc.description.abstractOBJECTIVES: Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility. METHODS: The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction. RESULTS: Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets. CONCLUSIONS: Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.-
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.titleGenome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in Asian populations-
dc.typeArticle-
dc.identifier.emailYang, J: jingy09@hku.hk-
dc.identifier.emailLau, WCS: cslau@hku.hk-
dc.identifier.emailChan, DTM: dtmchan@hku.hk-
dc.identifier.emailLee, TL: leetsz@hkucc.hku.hk-
dc.identifier.emailWong, SN: snwong@hkucc.hku.hk-
dc.identifier.emailHo, MHK: marcoho@hku.hk-
dc.identifier.emailLee, PPW: ppwlee@hku.hk-
dc.identifier.emailChung, BHY: bhychung@hku.hk-
dc.identifier.emailWong, RWS: rwswong@hkucc.hku.hk-
dc.identifier.emailMok, TMY: temy@hkucc.hku.hk-
dc.identifier.emailWong, WHS: whswong@hku.hk-
dc.identifier.emailWong, CM: jcmwong@hkucc.hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.emailGarcia-Barcelo, MM: mmgarcia@hku.hk-
dc.identifier.emailCherny, SS: cherny@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.emailYang, W: yangwl@hkucc.hku.hk-
dc.identifier.authorityLau, WCS=rp01348-
dc.identifier.authorityChan, DTM=rp00394-
dc.identifier.authorityLee, PPW=rp00462-
dc.identifier.authorityChung, BHY=rp00473-
dc.identifier.authorityMok, TMY=rp00490-
dc.identifier.authorityWong, CM=rp00231-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityGarcia-Barcelo, MM=rp00445-
dc.identifier.authorityCherny, SS=rp00232-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityLau, YL=rp00361-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.doi10.1136/annrheumdis-2014-206367-
dc.identifier.pmid25862617-
dc.identifier.hkuros244466-
dc.identifier.hkuros232401-
dc.publisher.placeUnited Kingdom-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats