Dataset Information

A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait.

ABSTRACT:

Objectives

To screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner.

Patients and methods

AS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina BeadStudio 3.2 software. PLINK package was used to remove non-autosomal SNPs and to further eliminate markers of typing errors. An affected-only linkage analysis was carried out using both non-parametric and parametric linkage analyses, as implemented in MERLIN.

Result

Seventy-eight AS patients (48 males and 30 females, mean age: 39±16 years) were enrolled in the study. The mean age of onset was 23±10 years and mean duration of disease was 16.7±12.2 years. Iritis (2/76, 2.86%), dactylitis (5/78, 6.41%), hip joint involvement (9/78, 11.54%), peripheral arthritis (22/78, 28.21%), inflammatory back pain (IBP) (69/78, 88.46%) and HLA-B27 positivity (70/78, 89.74%) were observed in these patients. Using non-parameter linkage analysis, we found one susceptibility locus for AS, IBP and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis. The identical susceptibility locus region spanning above 9.44Mb was detected in AS IBP and HLA-B27 by the parametric linkage analysis.

Conclusion

Our genome-wide SNP linkage analysis in ten families with ankylosing spondylitis suggests a susceptibility locus on 6p21 in AS, which is a risk locus for IBP in AS patients.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5156442 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait.

Zhang Yanli Y Liao Zetao Z Wei Qiujing Q Pan Yunfeng Y Wang Xinwei X Cao Shuangyan S Guo Zishi Z Wu Yuqiong Y Rong Ju J Jin Ou O Xu Manlong M Lin Zhiming Z Gu Jieruo J

PloS one 20161214 12

<h4>Objectives</h4>To screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner.<h4>Patients and methods</h4>AS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina ...[more]

PMID: 27973620

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Project description:Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6 × 10(-10), odds ratio (OR)?= 0.74, 95% CI:0.68-0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6 × 10(-4). OR = 0.86 (95% CI:0.79-0.93); rs744166, P = 2.6 × 10(-5), OR = 0.84 (95% CI:0.77-0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2 × 10(-5), OR = 0.65 (95% CI:0.54-0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2 × 10(-5), OR = 0.83 (95% CI:0.76-0.91)), CDKAL1 (rs6908425, P = 1.1 × 10(-4), OR = 0.82 (95% CI:0.74-0.91)), LRRK2/MUC19 (rs11175593, P = 9.9 × 10(-5), OR = 1.92 (95% CI: 1.38-2.67)), and chr13q14 (rs3764147, P =?5.9 × 10(-4), OR = 1.19 (95% CI: 1.08-1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases.

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Dataset Information

A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait.

Objectives

Patients and methods

Result

Conclusion

Publications

A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait.

Similar Datasets

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