A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis

Stephan Weidinger, Saffron A. G. Willis-Owen, Yoichiro Kamatani, Hansjörg Baurecht, Nilesh Morar, Liming Liang, Pauline Edser, Teresa Street, Elke Rodriguez, Grainne M. O'Regan, Paula Beattie, Regina Fölster-Holst, Andre Franke, Natalija Novak, Caoimhe M. Fahy, Mårten C G Winge, Michael Kabesch, Thomas Illig, Simon Heath, Cilla Söderhäll & 13 others Erik Melén, Göran Pershagen, Juha Kere, Maria Bradley, Agne Lieden, Magnus Nordenskjold, John I Harper, W. H. Irwin McLean, Sara J Brown, William O. C. Cookson, G. Mark Lathrop, Alan D. Irvine, Miriam F. Moffatt

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    Abstract

    Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.
    Original languageEnglish
    Pages (from-to)4841-4856
    Number of pages16
    JournalHuman Molecular Genetics
    Volume22
    Issue number23
    DOIs
    Publication statusPublished - Dec 2013

    Fingerprint

    Genome-Wide Association Study
    Atopic Dermatitis
    Psoriasis
    Asthma
    Single Nucleotide Polymorphism
    Chromosomes, Human, Pair 5
    Chromosomes, Human, Pair 11
    Chromosomes, Human, Pair 6
    Genetic Linkage
    Interleukin-13
    Chromosomes, Human, Pair 1
    Major Histocompatibility Complex
    Skin Diseases
    Alleles
    Genotype
    Genome

    Cite this

    Weidinger, S., Willis-Owen, S. A. G., Kamatani, Y., Baurecht, H., Morar, N., Liang, L., ... Moffatt, M. F. (2013). A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Human Molecular Genetics, 22(23), 4841-4856. https://doi.org/10.1093/hmg/ddt317
    Weidinger, Stephan ; Willis-Owen, Saffron A. G. ; Kamatani, Yoichiro ; Baurecht, Hansjörg ; Morar, Nilesh ; Liang, Liming ; Edser, Pauline ; Street, Teresa ; Rodriguez, Elke ; O'Regan, Grainne M. ; Beattie, Paula ; Fölster-Holst, Regina ; Franke, Andre ; Novak, Natalija ; Fahy, Caoimhe M. ; Winge, Mårten C G ; Kabesch, Michael ; Illig, Thomas ; Heath, Simon ; Söderhäll, Cilla ; Melén, Erik ; Pershagen, Göran ; Kere, Juha ; Bradley, Maria ; Lieden, Agne ; Nordenskjold, Magnus ; Harper, John I ; McLean, W. H. Irwin ; Brown, Sara J ; Cookson, William O. C. ; Lathrop, G. Mark ; Irvine, Alan D. ; Moffatt, Miriam F. / A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. In: Human Molecular Genetics. 2013 ; Vol. 22, No. 23. pp. 4841-4856.
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    abstract = "Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.",
    author = "Stephan Weidinger and Willis-Owen, {Saffron A. G.} and Yoichiro Kamatani and Hansj{\"o}rg Baurecht and Nilesh Morar and Liming Liang and Pauline Edser and Teresa Street and Elke Rodriguez and O'Regan, {Grainne M.} and Paula Beattie and Regina F{\"o}lster-Holst and Andre Franke and Natalija Novak and Fahy, {Caoimhe M.} and Winge, {M{\aa}rten C G} and Michael Kabesch and Thomas Illig and Simon Heath and Cilla S{\"o}derh{\"a}ll and Erik Mel{\'e}n and G{\"o}ran Pershagen and Juha Kere and Maria Bradley and Agne Lieden and Magnus Nordenskjold and Harper, {John I} and McLean, {W. H. Irwin} and Brown, {Sara J} and Cookson, {William O. C.} and Lathrop, {G. Mark} and Irvine, {Alan D.} and Moffatt, {Miriam F.}",
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    Weidinger, S, Willis-Owen, SAG, Kamatani, Y, Baurecht, H, Morar, N, Liang, L, Edser, P, Street, T, Rodriguez, E, O'Regan, GM, Beattie, P, Fölster-Holst, R, Franke, A, Novak, N, Fahy, CM, Winge, MCG, Kabesch, M, Illig, T, Heath, S, Söderhäll, C, Melén, E, Pershagen, G, Kere, J, Bradley, M, Lieden, A, Nordenskjold, M, Harper, JI, McLean, WHI, Brown, SJ, Cookson, WOC, Lathrop, GM, Irvine, AD & Moffatt, MF 2013, 'A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis', Human Molecular Genetics, vol. 22, no. 23, pp. 4841-4856. https://doi.org/10.1093/hmg/ddt317

    A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. / Weidinger, Stephan; Willis-Owen, Saffron A. G.; Kamatani, Yoichiro; Baurecht, Hansjörg; Morar, Nilesh; Liang, Liming; Edser, Pauline; Street, Teresa; Rodriguez, Elke; O'Regan, Grainne M.; Beattie, Paula; Fölster-Holst, Regina; Franke, Andre; Novak, Natalija; Fahy, Caoimhe M.; Winge, Mårten C G; Kabesch, Michael; Illig, Thomas; Heath, Simon; Söderhäll, Cilla; Melén, Erik; Pershagen, Göran; Kere, Juha; Bradley, Maria; Lieden, Agne; Nordenskjold, Magnus; Harper, John I; McLean, W. H. Irwin; Brown, Sara J; Cookson, William O. C.; Lathrop, G. Mark; Irvine, Alan D.; Moffatt, Miriam F. (Lead / Corresponding author).

    In: Human Molecular Genetics, Vol. 22, No. 23, 12.2013, p. 4841-4856.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis

    AU - Weidinger, Stephan

    AU - Willis-Owen, Saffron A. G.

    AU - Kamatani, Yoichiro

    AU - Baurecht, Hansjörg

    AU - Morar, Nilesh

    AU - Liang, Liming

    AU - Edser, Pauline

    AU - Street, Teresa

    AU - Rodriguez, Elke

    AU - O'Regan, Grainne M.

    AU - Beattie, Paula

    AU - Fölster-Holst, Regina

    AU - Franke, Andre

    AU - Novak, Natalija

    AU - Fahy, Caoimhe M.

    AU - Winge, Mårten C G

    AU - Kabesch, Michael

    AU - Illig, Thomas

    AU - Heath, Simon

    AU - Söderhäll, Cilla

    AU - Melén, Erik

    AU - Pershagen, Göran

    AU - Kere, Juha

    AU - Bradley, Maria

    AU - Lieden, Agne

    AU - Nordenskjold, Magnus

    AU - Harper, John I

    AU - McLean, W. H. Irwin

    AU - Brown, Sara J

    AU - Cookson, William O. C.

    AU - Lathrop, G. Mark

    AU - Irvine, Alan D.

    AU - Moffatt, Miriam F.

    PY - 2013/12

    Y1 - 2013/12

    N2 - Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.

    AB - Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.

    U2 - 10.1093/hmg/ddt317

    DO - 10.1093/hmg/ddt317

    M3 - Article

    VL - 22

    SP - 4841

    EP - 4856

    JO - Human Molecular Genetics

    JF - Human Molecular Genetics

    SN - 0964-6906

    IS - 23

    ER -