Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.
| Original language | English |
|---|---|
| Article number | 6046 |
| Journal | Nature Communications |
| Volume | 6 |
| DOIs | |
| Publication status | Published - 2015 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. / Bowes, John; Budu-Aggrey, Ashley; Huffmeier, Ulrike; Uebe, Steffen; Steel, Kathryn; Hebert, Harry L.; Wallace, Chris; Massey, Jonathan; Bruce, Ian N.; Bluett, James; Feletar, Marie; Morgan, Ann W.; Marzo-Ortega, Helena; Donohoe, Gary; Morris, Derek W.; Helliwell, Philip; Ryan, Anthony W.; Kane, David; Warren, Richard B.; Korendowych, Eleanor; Alenius, Gerd Marie; Giardina, Emiliano; Packham, Jonathan; McManus, Ross; Fitzgerald, Oliver; McHugh, Neil; Brown, Matthew A.; Ho, Pauline; Behrens, Frank; Burkhardt, Harald; Reis, Andre; Barton, Anne.
In: Nature Communications, Vol. 6, 6046, 2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis
AU - Bowes, John
AU - Budu-Aggrey, Ashley
AU - Huffmeier, Ulrike
AU - Uebe, Steffen
AU - Steel, Kathryn
AU - Hebert, Harry L.
AU - Wallace, Chris
AU - Massey, Jonathan
AU - Bruce, Ian N.
AU - Bluett, James
AU - Feletar, Marie
AU - Morgan, Ann W.
AU - Marzo-Ortega, Helena
AU - Donohoe, Gary
AU - Morris, Derek W.
AU - Helliwell, Philip
AU - Ryan, Anthony W.
AU - Kane, David
AU - Warren, Richard B.
AU - Korendowych, Eleanor
AU - Alenius, Gerd Marie
AU - Giardina, Emiliano
AU - Packham, Jonathan
AU - McManus, Ross
AU - Fitzgerald, Oliver
AU - McHugh, Neil
AU - Brown, Matthew A.
AU - Ho, Pauline
AU - Behrens, Frank
AU - Burkhardt, Harald
AU - Reis, Andre
AU - Barton, Anne
PY - 2015
Y1 - 2015
N2 - Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.
AB - Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.
UR - http://www.scopus.com/inward/record.url?scp=84923253404&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923253404&partnerID=8YFLogxK
U2 - 10.1038/ncomms7046
DO - 10.1038/ncomms7046
M3 - Article
AN - SCOPUS:84923253404
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 6046
ER -