title: A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Zetao
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Shuangyan
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Zishi
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Rong
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ou
authors.initials: O
authors.lastname: Jin
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Manlong
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Zhiming
authors.identifier: http://orcid.org/0000-0003-0153-607X
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jieruo
authors.initials: J
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001416:Back Pain / Q000235:genetics*; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D055815:Young Adult
chemical_list: D015796:HLA-B27 Antigen