A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

Abstract

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.

ERAP1/ERAP2 and RUNX3 polymorphisms are not associated with ankylosing spondylitis susceptibility in Chinese Han

“…As mentioned above, combining earlier data from Lin et al . 25 with our results showed that there is no significant association of ERAP1/ERAP2 polymorphisms and the risk of AS in Chinese Han. The reason for this discrepancy is unclear, and may be due to as yet unknown environmental factors.…”

“…However, our meta‐analysis of all data reported on the association of polymorphisms in these genes with AS indicated that population and geographical differences might be one of the causes of heterogeneity. Even in Asian populations, the association of ERAP1 gene polymorphisms with AS differs depending on the studied populations 25, 30, 34. Results of studies from Korea and Taiwan were similar, but different from data from mainland China.…”

“…A literature search in the PubMed database resulted in the identification of 22 studies; 12 studies met the study inclusion criteria, including four studies from European populations and eight studies from Asian populations (two from Korean, six from Chinese populations), including the present study 9, 25, 26, 30, 31, 34, 35, 37, 38, 39, 40. Ten studies were excluded (seven studies due to lack of data and three studies having duplicate data).…”

“…The SNPs rs27037, rs27980 and rs27582 were reported to be in strong linkage disequilibrium (LD), as well as the SNPs rs30187 and rs27434 and the SNPs rs2549782 and rs2248374. Based on conflicting results in several studies 9, 10, 24, 25, 26, all sites were selected for the current study (Fig. 1).…”

Association of mineralization-related genes TNAP and ANKH polymorphisms with ankylosing spondylitis in the Chinese Han population

“…Most previously identified genetic risk variants for AS are related to the immune response. Until recently, in a GWAS study in the Chinese Han population, Gu et al (2) discovered two new susceptibility loci rs4552569 and rs17095830 near genes (between HAPLN1-EDIL3 at 5q14.3 and within ANO6 at 12q12) related to cartilage development and bone formation. Our previous study also identified a novel single nucleotide polymorphism (SNP) site (c.4488+74 G > A) in low-density lipoprotein receptor-related protein 5 (LRP5) gene was associated with AS in the Chinese Han population (3).…”