Genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent (69 Australian, 1129 British and 983 North American) and 5,140 ethnically matched controls derived from British Birth Cohort genotyped by WTCC (1436) and Illumina iControlDB database (4149). HapMAP CEU (North & Western European), YRI (Nigeria), JPT (Japan), CHB(Chinese) samples (262) were added to the control to use for quality control. Genotyping was performed with Illumina HumHap370 genotyping chips and 288,662 SNPs were available for analysis. Imputation analyses were carried out with MACH, using phased data from CEU invidividuals from release 22 of HapMap project.    Replication was performed by IPLEX technology or by KASPar technology in an independent cohort of 898 British ankylosing spondylitis cases and 1,518 unselected British controls.This study reports four novel genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.

Study Type
Whole Genome Association Study
Exclusion Criteria

Samples Exclusion: Related individuals (410 samples) containing 62 cases and 135 of the HapMap quality-control samples that consisted of related members of family trios. 

SNP Exclusion: All SNPs with quality scores < 0.15, all individuals with <98% genotyping success, and SNPs with poor cluster plots were excluded from analysis.
Outliers in a plot of heterozygosity versus missingness were excluded (n = 122, containing 29 cases).
SNPs with minor allele frequency < 1% (n = 135) or missingness > 5% (n = 2,226) and those not in Hardy-Weinberg equilibrium (P < 10−7, n = 11,337) were excluded.

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p31.3chr1:67128876-67302310IL23R  rs11209026G > A0.0629.10e-14C1.89 (1.56-2.27)D
2p15chr2:62238413-62405459rs4672495A > C0.3303.20e-09C1.18 (1.09-1.27)D
2p15chr2:62256286-62420888rs10865331G > A0.4001.90e-19C1.27 (1.18-1.37)D
2q11.2chr2:101678428-102080305IL1R2  rs2310173C > A0.4504.80e-07C1.18 (1.10-1.27)D
4q21.21chr4:79783694-80069700ANTXR2  rs4333130A > G0.3609.30e-08C1.22 (1.12-1.32)D
5q15chr5:96638641-97038254ERAP1  rs27037C > A0.2908.20e-11C1.23 (1.14-1.33)D
5q15chr5:96647765-97039314ERAP1  rs27434G > A0.2305.30e-12C1.19 (1.10-1.30)D
21q22.2chr21:39081110-39111851rs2242944G > A0.3708.30e-20C1.39 (1.28-1.49)D


GDXHsS00012 meets the following criteria:

Criteria Name
Disease Tags
Study for a Disease 


PMIDTitleFirst AuthorJournalDisease(s)Date