Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis
Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.684326/full |
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doaj-be5b01fa959f4f46af42fb1812d00ced |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Richard Ahn Richard Ahn Damjan Vukcevic Damjan Vukcevic Damjan Vukcevic Allan Motyer Allan Motyer Joanne Nititham David McG. Squire David McG. Squire Jill A. Hollenbach Paul J. Norman Eva Ellinghaus Rajan P. Nair Lam C. Tsoi Lam C. Tsoi Lam C. Tsoi Jorge Oksenberg John Foerster Wolfgang Lieb Stephan Weidinger Andre Franke James T. Elder James T. Elder Eric Jorgenson Stephen Leslie Stephen Leslie Stephen Leslie Wilson Liao |
| spellingShingle |
Richard Ahn Richard Ahn Damjan Vukcevic Damjan Vukcevic Damjan Vukcevic Allan Motyer Allan Motyer Joanne Nititham David McG. Squire David McG. Squire Jill A. Hollenbach Paul J. Norman Eva Ellinghaus Rajan P. Nair Lam C. Tsoi Lam C. Tsoi Lam C. Tsoi Jorge Oksenberg John Foerster Wolfgang Lieb Stephan Weidinger Andre Franke James T. Elder James T. Elder Eric Jorgenson Stephen Leslie Stephen Leslie Stephen Leslie Wilson Liao Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis Frontiers in Immunology psoriasis KIR HLA imputation genetics autoimmunity |
| author_facet |
Richard Ahn Richard Ahn Damjan Vukcevic Damjan Vukcevic Damjan Vukcevic Allan Motyer Allan Motyer Joanne Nititham David McG. Squire David McG. Squire Jill A. Hollenbach Paul J. Norman Eva Ellinghaus Rajan P. Nair Lam C. Tsoi Lam C. Tsoi Lam C. Tsoi Jorge Oksenberg John Foerster Wolfgang Lieb Stephan Weidinger Andre Franke James T. Elder James T. Elder Eric Jorgenson Stephen Leslie Stephen Leslie Stephen Leslie Wilson Liao |
| author_sort |
Richard Ahn |
| title |
Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis |
| title_short |
Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis |
| title_full |
Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis |
| title_fullStr |
Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis |
| title_full_unstemmed |
Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis |
| title_sort |
large-scale imputation of kir copy number and hla alleles in north american and european psoriasis case-control cohorts reveals association of inhibitory kir2dl2 with psoriasis |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2021-06-01 |
| description |
Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense required for direct genotyping of KIR genes. Here, we implemented KIR*IMP to impute KIR copy number from single-nucleotide polymorphisms (SNPs) on chromosome 19 in the discovery cohort (n=11,912) from the PAGE consortium, University of California San Francisco, and the University of Dundee, and in a replication cohort (n=66,357) from Kaiser Permanente Northern California. Stratified multivariate logistic regression that accounted for patient ancestry and high-risk HLA alleles revealed that KIR2DL2 copy number was significantly associated with psoriasis in the discovery cohort (p ≤ 0.05). The KIR2DL2 copy number association was replicated in the Kaiser Permanente replication cohort. This is the first reported association of KIR2DL2 copy number with psoriasis and highlights the importance of KIR genetics in the pathogenesis of psoriasis. |
| topic |
psoriasis KIR HLA imputation genetics autoimmunity |
| url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.684326/full |
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1721381909504720896 |
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doaj-be5b01fa959f4f46af42fb1812d00ced2021-06-11T16:53:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.684326684326Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With PsoriasisRichard Ahn0Richard Ahn1Damjan Vukcevic2Damjan Vukcevic3Damjan Vukcevic4Allan Motyer5Allan Motyer6Joanne Nititham7David McG. Squire8David McG. Squire9Jill A. Hollenbach10Paul J. Norman11Eva Ellinghaus12Rajan P. Nair13Lam C. Tsoi14Lam C. Tsoi15Lam C. Tsoi16Jorge Oksenberg17John Foerster18Wolfgang Lieb19Stephan Weidinger20Andre Franke21James T. Elder22James T. Elder23Eric Jorgenson24Stephen Leslie25Stephen Leslie26Stephen Leslie27Wilson Liao28Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United StatesInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, United StatesMelbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, AustraliaSchool of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, AustraliaClinical Epidemiology and Biostatistics Unit, Murdoch Children’s Research Institute, Parkville, VIC, AustraliaMelbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, AustraliaSchool of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Dermatology, University of California, San Francisco, San Francisco, CA, United StatesMelbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, AustraliaSchool of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United StatesDivision of Personalized Medicine, Department of Immunology and Microbiology, University of Colorado, San Francisco, CA, United StatesInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany0Department of Dermatology, University of Michigan, Ann Arbor, MI, United States0Department of Dermatology, University of Michigan, Ann Arbor, MI, United States1Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States2Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, United StatesDepartment of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States3College of Medicine, Dentistry, and Nursing, University of Dundee, Dundee, United Kingdom4Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany5Department of Dermatology, University Hospital Schleswig Holstein, Kiel, GermanyInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany0Department of Dermatology, University of Michigan, Ann Arbor, MI, United States6Ann Arbor Veterans Affairs Hospital, Dermatology, Ann Arbor, MI, United States7Division of Research, Kaiser Permanente, Oakland, CA, United StatesMelbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, AustraliaSchool of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia8School of Biosciences, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Dermatology, University of California, San Francisco, San Francisco, CA, United StatesKiller cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense required for direct genotyping of KIR genes. Here, we implemented KIR*IMP to impute KIR copy number from single-nucleotide polymorphisms (SNPs) on chromosome 19 in the discovery cohort (n=11,912) from the PAGE consortium, University of California San Francisco, and the University of Dundee, and in a replication cohort (n=66,357) from Kaiser Permanente Northern California. Stratified multivariate logistic regression that accounted for patient ancestry and high-risk HLA alleles revealed that KIR2DL2 copy number was significantly associated with psoriasis in the discovery cohort (p ≤ 0.05). The KIR2DL2 copy number association was replicated in the Kaiser Permanente replication cohort. This is the first reported association of KIR2DL2 copy number with psoriasis and highlights the importance of KIR genetics in the pathogenesis of psoriasis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.684326/fullpsoriasisKIRHLAimputationgeneticsautoimmunity |