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Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis

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Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis. / Knight, Jo; Spain, Sarah L.; Capon, Francesca et al.

In: Human Molecular Genetics, Vol. 21, No. 23, 01.12.2012, p. 5185-5192.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Knight, J, Spain, SL, Capon, F, Hayday, A, Nestle, FO, Clop, A, Barker, JNWN, Weale, ME, Trembath, RC & Wellcome Trust Case Control Consortium 2012, 'Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis', Human Molecular Genetics, vol. 21, no. 23, pp. 5185-5192. https://doi.org/10.1093/hmg/dds344

APA

Knight, J., Spain, S. L., Capon, F., Hayday, A., Nestle, F. O., Clop, A., Barker, J. N. W. N., Weale, M. E., Trembath, R. C., & Wellcome Trust Case Control Consortium (2012). Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis. Human Molecular Genetics, 21(23), 5185-5192. https://doi.org/10.1093/hmg/dds344

Vancouver

Knight J, Spain SL, Capon F, Hayday A, Nestle FO, Clop A et al. Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis. Human Molecular Genetics. 2012 Dec 1;21(23):5185-5192. Epub 2012 Aug 21. doi: 10.1093/hmg/dds344

Author

Knight, Jo ; Spain, Sarah L. ; Capon, Francesca et al. / Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 23. pp. 5185-5192.

Bibtex

@article{6da18cea0137498388ab3b40881ceeac,
title = "Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis",
abstract = "Psoriasis is a common, chronic, inflammatory skin disorder. A number of genetic loci have been shown to confer risk for psoriasis. Collectively, these offer an integrated model for the inherited basis for susceptibility to psoriasis that combines altered skin barrier function together with the dysregulation of innate immune pathogen sensing and adap-tive immunity. The major histocompatibility complex (MHC) harbours the psoriasis susceptibility region which exhibits the largest effect size, driven in part by variation contained on the HLA-Cw*0602 allele. However, the resolution of the number and genomic location of potential independent risk loci are hampered by extensive linkage disequilibrium across the region. We leveraged the power of large psoriasis case and control data sets and the statistical approach of conditional analysis to identify potential further association signals distributed across the MHC. In addition to the major loci at HLA-C (P = 2.20 × 10(-236)), we observed and replicated four additional independent signals for disease association, three of which are novel. We detected evidence for association at SNPs rs2507971 (P = 6.73 × 10(-14)), rs9260313 (P = 7.93 × 10(-09)), rs66609536 (P = 3.54 × 10(-07)) and rs380924 (P = 6.24 × 10(-06)), located within the class I region of the MHC, with each observation replicated in an independent sample (P ≤ 0.01). The previously identified locus is close to MICA, the other three lie near MICB, HLA-A and HCG9 (a non-coding RNA gene). The identification of disease associations with both MICA and MICB is particularly intriguing, since each encodes an MHC class I-related protein with potent immunological function.",
keywords = "Alleles, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-C Antigens, Humans, Major Histocompatibility Complex, Polymorphism, Single Nucleotide, Psoriasis",
author = "Jo Knight and Spain, {Sarah L.} and Francesca Capon and Adrian Hayday and Nestle, {Frank O.} and Alex Clop and Barker, {Jonathan N. W. N.} and Weale, {Michael E.} and Trembath, {Richard C.} and {Wellcome Trust Case Control Consortium}",
year = "2012",
month = dec,
day = "1",
doi = "10.1093/hmg/dds344",
language = "English",
volume = "21",
pages = "5185--5192",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "23",

}

RIS

TY - JOUR

T1 - Conditional analysis identifies three novel major histocompatibility complex loci associated with psoriasis

AU - Knight, Jo

AU - Spain, Sarah L.

AU - Capon, Francesca

AU - Hayday, Adrian

AU - Nestle, Frank O.

AU - Clop, Alex

AU - Barker, Jonathan N. W. N.

AU - Weale, Michael E.

AU - Trembath, Richard C.

AU - Wellcome Trust Case Control Consortium

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Psoriasis is a common, chronic, inflammatory skin disorder. A number of genetic loci have been shown to confer risk for psoriasis. Collectively, these offer an integrated model for the inherited basis for susceptibility to psoriasis that combines altered skin barrier function together with the dysregulation of innate immune pathogen sensing and adap-tive immunity. The major histocompatibility complex (MHC) harbours the psoriasis susceptibility region which exhibits the largest effect size, driven in part by variation contained on the HLA-Cw*0602 allele. However, the resolution of the number and genomic location of potential independent risk loci are hampered by extensive linkage disequilibrium across the region. We leveraged the power of large psoriasis case and control data sets and the statistical approach of conditional analysis to identify potential further association signals distributed across the MHC. In addition to the major loci at HLA-C (P = 2.20 × 10(-236)), we observed and replicated four additional independent signals for disease association, three of which are novel. We detected evidence for association at SNPs rs2507971 (P = 6.73 × 10(-14)), rs9260313 (P = 7.93 × 10(-09)), rs66609536 (P = 3.54 × 10(-07)) and rs380924 (P = 6.24 × 10(-06)), located within the class I region of the MHC, with each observation replicated in an independent sample (P ≤ 0.01). The previously identified locus is close to MICA, the other three lie near MICB, HLA-A and HCG9 (a non-coding RNA gene). The identification of disease associations with both MICA and MICB is particularly intriguing, since each encodes an MHC class I-related protein with potent immunological function.

AB - Psoriasis is a common, chronic, inflammatory skin disorder. A number of genetic loci have been shown to confer risk for psoriasis. Collectively, these offer an integrated model for the inherited basis for susceptibility to psoriasis that combines altered skin barrier function together with the dysregulation of innate immune pathogen sensing and adap-tive immunity. The major histocompatibility complex (MHC) harbours the psoriasis susceptibility region which exhibits the largest effect size, driven in part by variation contained on the HLA-Cw*0602 allele. However, the resolution of the number and genomic location of potential independent risk loci are hampered by extensive linkage disequilibrium across the region. We leveraged the power of large psoriasis case and control data sets and the statistical approach of conditional analysis to identify potential further association signals distributed across the MHC. In addition to the major loci at HLA-C (P = 2.20 × 10(-236)), we observed and replicated four additional independent signals for disease association, three of which are novel. We detected evidence for association at SNPs rs2507971 (P = 6.73 × 10(-14)), rs9260313 (P = 7.93 × 10(-09)), rs66609536 (P = 3.54 × 10(-07)) and rs380924 (P = 6.24 × 10(-06)), located within the class I region of the MHC, with each observation replicated in an independent sample (P ≤ 0.01). The previously identified locus is close to MICA, the other three lie near MICB, HLA-A and HCG9 (a non-coding RNA gene). The identification of disease associations with both MICA and MICB is particularly intriguing, since each encodes an MHC class I-related protein with potent immunological function.

KW - Alleles

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - HLA-C Antigens

KW - Humans

KW - Major Histocompatibility Complex

KW - Polymorphism, Single Nucleotide

KW - Psoriasis

U2 - 10.1093/hmg/dds344

DO - 10.1093/hmg/dds344

M3 - Journal article

C2 - 22914738

VL - 21

SP - 5185

EP - 5192

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 23

ER -