Genome-wide association study of recalcitrant atopic dermatitis in Korean children

Kyung Won Kim, Rachel A. Myers, Ji Hyun Lee, Catherine Igartua, Kyung Eun Lee, Yoon Hee Kim, Eun Jin Kim, Dankyu Yoon, Joo Shil Lee, Tomomitsu Hirota, Mayumi Tamari, Atsushi Takahashi, Michiaki Kubo, Je Min Choi, Kyu Earn Kim, Dan L. Nicolae, Carole Ober, Myung Hyun Sohn

Research output: Contribution to journalArticle

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Abstract

Background Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. Objective We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization. Methods Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks. Results SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10-8). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10-6, including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells. Conclusion Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis.

Original languageEnglish
Pages (from-to)678-684.e4
JournalJournal of Allergy and Clinical Immunology
Volume136
Issue number3
DOIs
Publication statusPublished - 01-09-2015

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Genome-Wide Association Study
Atopic Dermatitis
Single Nucleotide Polymorphism
Immunoglobulin E
Genes
Protein Phosphatase 1
Cyclin A
Quantitative Trait Loci
Phosphoprotein Phosphatases
Neuroblastoma
S Phase
Skin Diseases
Proline
Quality Control
Thymus Gland
Epithelial Cells
Genome

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kim, K. W., Myers, R. A., Lee, J. H., Igartua, C., Lee, K. E., Kim, Y. H., ... Sohn, M. H. (2015). Genome-wide association study of recalcitrant atopic dermatitis in Korean children. Journal of Allergy and Clinical Immunology, 136(3), 678-684.e4. https://doi.org/10.1016/j.jaci.2015.03.030
Kim, Kyung Won ; Myers, Rachel A. ; Lee, Ji Hyun ; Igartua, Catherine ; Lee, Kyung Eun ; Kim, Yoon Hee ; Kim, Eun Jin ; Yoon, Dankyu ; Lee, Joo Shil ; Hirota, Tomomitsu ; Tamari, Mayumi ; Takahashi, Atsushi ; Kubo, Michiaki ; Choi, Je Min ; Kim, Kyu Earn ; Nicolae, Dan L. ; Ober, Carole ; Sohn, Myung Hyun. / Genome-wide association study of recalcitrant atopic dermatitis in Korean children. In: Journal of Allergy and Clinical Immunology. 2015 ; Vol. 136, No. 3. pp. 678-684.e4.
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abstract = "Background Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. Objective We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization. Methods Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks. Results SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10-8). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10-6, including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells. Conclusion Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis.",
author = "Kim, {Kyung Won} and Myers, {Rachel A.} and Lee, {Ji Hyun} and Catherine Igartua and Lee, {Kyung Eun} and Kim, {Yoon Hee} and Kim, {Eun Jin} and Dankyu Yoon and Lee, {Joo Shil} and Tomomitsu Hirota and Mayumi Tamari and Atsushi Takahashi and Michiaki Kubo and Choi, {Je Min} and Kim, {Kyu Earn} and Nicolae, {Dan L.} and Carole Ober and Sohn, {Myung Hyun}",
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Kim, KW, Myers, RA, Lee, JH, Igartua, C, Lee, KE, Kim, YH, Kim, EJ, Yoon, D, Lee, JS, Hirota, T, Tamari, M, Takahashi, A, Kubo, M, Choi, JM, Kim, KE, Nicolae, DL, Ober, C & Sohn, MH 2015, 'Genome-wide association study of recalcitrant atopic dermatitis in Korean children', Journal of Allergy and Clinical Immunology, vol. 136, no. 3, pp. 678-684.e4. https://doi.org/10.1016/j.jaci.2015.03.030

Genome-wide association study of recalcitrant atopic dermatitis in Korean children. / Kim, Kyung Won; Myers, Rachel A.; Lee, Ji Hyun; Igartua, Catherine; Lee, Kyung Eun; Kim, Yoon Hee; Kim, Eun Jin; Yoon, Dankyu; Lee, Joo Shil; Hirota, Tomomitsu; Tamari, Mayumi; Takahashi, Atsushi; Kubo, Michiaki; Choi, Je Min; Kim, Kyu Earn; Nicolae, Dan L.; Ober, Carole; Sohn, Myung Hyun.

In: Journal of Allergy and Clinical Immunology, Vol. 136, No. 3, 01.09.2015, p. 678-684.e4.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study of recalcitrant atopic dermatitis in Korean children

AU - Kim, Kyung Won

AU - Myers, Rachel A.

AU - Lee, Ji Hyun

AU - Igartua, Catherine

AU - Lee, Kyung Eun

AU - Kim, Yoon Hee

AU - Kim, Eun Jin

AU - Yoon, Dankyu

AU - Lee, Joo Shil

AU - Hirota, Tomomitsu

AU - Tamari, Mayumi

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Choi, Je Min

AU - Kim, Kyu Earn

AU - Nicolae, Dan L.

AU - Ober, Carole

AU - Sohn, Myung Hyun

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Background Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. Objective We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization. Methods Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks. Results SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10-8). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10-6, including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells. Conclusion Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis.

AB - Background Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. Objective We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization. Methods Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks. Results SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10-8). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10-6, including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells. Conclusion Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis.

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