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

Z Lin, JX Bei, M Shen, Q Li, Z Liao, Y Zhang, Q Lv… - Nature …, 2012 - nature.com
Z Lin, JX Bei, M Shen, Q Li, Z Liao, Y Zhang, Q Lv, Q Wei, HQ Low, YM Guo, S Cao, M Yang…
Nature genetics, 2012nature.com
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; …
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.
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