Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene
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Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene. / Pointon, J. J.; Harvey, D.; Karaderi, T.; Appleton, L. H.; Farrar, C.; Stone, M. A.; Sturrock, R. D.; Brown, M. A.; Wordsworth, B. P.
I: Genes and Immunity, Bind 11, Nr. 6, 01.01.2010, s. 490-496.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene
AU - Pointon, J. J.
AU - Harvey, D.
AU - Karaderi, T.
AU - Appleton, L. H.
AU - Farrar, C.
AU - Stone, M. A.
AU - Sturrock, R. D.
AU - Brown, M. A.
AU - Wordsworth, B. P.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Ankylosing spondylitis (AS) is polygenic with contributions from the immunologically relevant genes HLA-B27, ERAP1 and IL23R. A recent genome-wide association screen (GWAS) identified associations (P0.005) with the non-synonymous single-nucleotide polymorphisms (nsSNPs), rs4077515 and rs3812571, in caspase recruitment domain-containing protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) on chromosome 9q that had previously been linked to AS. We replicated these associations in a study of 730 AS patients compared with 2879 historic disease controls (rs4077515 P0.0004, odds ratio (OR)1.2, 95% confidence interval (CI)1.1-1.4; rs3812571 P0.0003, OR1.2, 95% CI1.1-1.4). Meta-analysis revealed strong associations of both SNPs with AS, rs4077515 P0.000005, OR1.2, 95% CI1.1-1.3 and rs3812571 P0.000006, OR1.2, 95% CI1.1-1.3. We then typed 1604 AS cases and 1020 controls for 13 tagging SNPs; 6 showed at least nominal association, 5 of which were in CARD9. We imputed genotypes for 13 additional SNPs but none was more strongly associated with AS than the tagging SNPs. Finally, interrogation of an mRNA expression database revealed that the SNPs most strongly associated with AS (or in strong linkage disequilibrium) were those most associated with CARD9 expression. CARD9 is a plausible candidate for AS given its central role in the innate immune response.
AB - Ankylosing spondylitis (AS) is polygenic with contributions from the immunologically relevant genes HLA-B27, ERAP1 and IL23R. A recent genome-wide association screen (GWAS) identified associations (P0.005) with the non-synonymous single-nucleotide polymorphisms (nsSNPs), rs4077515 and rs3812571, in caspase recruitment domain-containing protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) on chromosome 9q that had previously been linked to AS. We replicated these associations in a study of 730 AS patients compared with 2879 historic disease controls (rs4077515 P0.0004, odds ratio (OR)1.2, 95% confidence interval (CI)1.1-1.4; rs3812571 P0.0003, OR1.2, 95% CI1.1-1.4). Meta-analysis revealed strong associations of both SNPs with AS, rs4077515 P0.000005, OR1.2, 95% CI1.1-1.3 and rs3812571 P0.000006, OR1.2, 95% CI1.1-1.3. We then typed 1604 AS cases and 1020 controls for 13 tagging SNPs; 6 showed at least nominal association, 5 of which were in CARD9. We imputed genotypes for 13 additional SNPs but none was more strongly associated with AS than the tagging SNPs. Finally, interrogation of an mRNA expression database revealed that the SNPs most strongly associated with AS (or in strong linkage disequilibrium) were those most associated with CARD9 expression. CARD9 is a plausible candidate for AS given its central role in the innate immune response.
KW - genetic association
KW - innate immunity
KW - spondyloarthropathy
UR - http://www.scopus.com/inward/record.url?scp=77956344915&partnerID=8YFLogxK
U2 - 10.1038/gene.2010.17
DO - 10.1038/gene.2010.17
M3 - Journal article
C2 - 20463747
AN - SCOPUS:77956344915
VL - 11
SP - 490
EP - 496
JO - Genes and Immunity
JF - Genes and Immunity
SN - 1466-4879
IS - 6
ER -
ID: 226397038