Genome-Wide Association Study for Serum Complement C3 and C4 Levels in Healthy Chinese Subjects

Xiaobo Yang, Jielin Sun, Yong Gao, Aihua Tan, Haiying Zhang, Yanling Hu, Junjie Feng, Xue Qin, Sha Tao, Zhuo Chen, Seong Tae Kim, Tao Peng, Ming Liao, Xiaoling Lin, Zengfeng Zhang, Minzhong Tang, Li Li, Linjian Mo, Zhengjia Liang, Deyi ShiZhang Huang, Xianghua Huang, Ming Liu, Qian Liu, Shijun Zhang, Jeffrey M. Trent, S. Lilly Zheng, Jianfeng Xu, Zengnan Mo

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Complement C3 and C4 play key roles in the main physiological activities of complement system, and their deficiencies or over-expression are associated with many clinical infectious or immunity diseases. A two-stage genome-wide association study (GWAS) was performed for serum levels of C3 and C4. The first stage was conducted in 1,999 healthy Chinese men, and the second stage was performed in an additional 1,496 subjects. We identified two SNPs, rs3753394 in CFH gene and rs3745567 in C3 gene, that are significantly associated with serum C3 levels at a genome-wide significance level (P = 7.33×10-11 and P = 1.83×10-9, respectively). For C4, one large genomic region on chromosome 6p21.3 is significantly associated with serum C4 levels. Two SNPs (rs1052693 and rs11575839) were located in the MHC class I area that include HLA-A, HLA-C, and HLA-B genes. Two SNPs (rs2075799 and rs2857009) were located 5′ and 3′ of C4 gene. The other four SNPs, rs2071278, rs3763317, rs9276606, and rs241428, were located in the MHC class II region that includes HLA-DRA, HLA-DRB, and HLA-DQB genes. The combined P-values for those eight SNPs ranged from 3.19×10-22 to 5.62×10-97. HBsAg-positive subjects have significantly lower C3 and C4 protein concentrations compared with HBsAg-negative subjects (P<0.05). Our study is the first GWAS report which shows genetic components influence the levels of complement C3 and C4. Our significant findings provide novel insights of their related autoimmune, infectious diseases, and molecular mechanisms.

Original languageEnglish (US)
Article numbere1002916
JournalPLoS genetics
Issue number9
StatePublished - Sep 2012
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research


Dive into the research topics of 'Genome-Wide Association Study for Serum Complement C3 and C4 Levels in Healthy Chinese Subjects'. Together they form a unique fingerprint.

Cite this