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

A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait.
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Zhang Y, Liao Z, Wei Q, Pan Y, Wang X, Cao S, Guo Z, Wu Y, Rong J, Jin O, Xu M, Lin Z, Gu J,


Zhang Y, Liao Z, Wei Q, Pan Y, Wang X, Cao S, Guo Z, Wu Y, Rong J, Jin O, Xu M, Lin Z, Gu J, (click to view)

Zhang Y, Liao Z, Wei Q, Pan Y, Wang X, Cao S, Guo Z, Wu Y, Rong J, Jin O, Xu M, Lin Z, Gu J,

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PloS one 2016 12 1411(12) e0166888 doi 10.1371/journal.pone.0166888
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.

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