TY - JOUR
T1 - Genome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in asian populations
AU - Zhang, Yan
AU - Yang, Jing
AU - Zhang, Jing
AU - Sun, Liangdan
AU - Hirankarn, Nattiya
AU - Pan, Hai Feng
AU - Lau, Chak Sing
AU - Chan, Tak Mao
AU - Lee, Tsz Leung
AU - Leung, Alexander Moon Ho
AU - Mok, Chi Chiu
AU - Zhang, Lu
AU - Wang, Yongfei
AU - Shen, Jiangshan Jane
AU - Wong, Sik Nin
AU - Lee, Ka Wing
AU - Ho, Marco Hok Kung
AU - Lee, Pamela Pui Wah
AU - Chung, Brian Hon Yin
AU - Chong, Chun Yin
AU - Wong, Raymond Woon Sing
AU - Mok, Mo Yin
AU - Wong, Wilfred Hing Sang
AU - Tong, Kwok Lung
AU - Tse, Niko Kei Chiu
AU - Li, Xiang Pei
AU - Avihingsanon, Yingyos
AU - Rianthavorn, Pornpimol
AU - Deekajorndej, Thavatchai
AU - Suphapeetiporn, Kanya
AU - Shotelersuk, Vorasuk
AU - Ying, Shirley King Yee
AU - Fung, Samuel Ka Shun
AU - Lai, Wai Ming
AU - Wong, Chun Ming
AU - Ng, Irene Oi Lin
AU - Garcia-Barcelo, Maria Merce
AU - Cherny, Stacey S.
AU - Cui, Yong
AU - Sham, Pak Chung
AU - Yang, Sen
AU - Ye, Dong Qing
AU - Zhang, Xue Jun
AU - Lau, Yu Lung
AU - Yang, Wanling
N1 - The authors thank Winnie Lau and her team for collection of samples and clinical records for Hong Kong patients. WY and YLL thank the Research Grant Council of Hong Kong (GRF 17125114, HKU783813M, HKU781709M, HKU 784611M, and HKU 770411M) for support. The authors also thank the S K Yee Medical Foundation general award (to BH-YC, YLL and WY) for support.
Publisher Copyright:
© 2016 Published by Elsevier Inc. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
PY - 2016/5
Y1 - 2016/5
N2 - Objectives: 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 genomewide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.
AB - Objectives: 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 genomewide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.
UR - https://www.scopus.com/pages/publications/84963529456
UR - https://www.sciencedirect.com/science/article/abs/pii/S0003496724018867?via%3Dihub
U2 - 10.1136/annrheumdis-2014-206367
DO - 10.1136/annrheumdis-2014-206367
M3 - Journal article
C2 - 25862617
AN - SCOPUS:84963529456
SN - 0003-4967
VL - 75
SP - 891
EP - 898
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 5
ER -
SDG 3 Good Health and Well-being