Meta-analysis identifies seven susceptibility loci involved in the atopic March

I. Marenholz; J. Esparza-Gordillo; F. Rüschendorf; A. Bauerfeind; D.P. Strachan; B.D. Spycher; H. Baurecht; P. Margaritte-Jeannin; A. Sääf; M. Kerkhof; M. Ege; Svetlana Baltic; M.C. Matheson; J. Li; S. Michel; Wei Ang; W. Mcardle; A. Arnold; G. Homuth; F. Demenais; E. Bouzigon; C. Söderhäll; G. Pershagen; J.C. De Jongste; D.S. Postma; C. Braun-Fahrländer; E. Horak; L.M. Ogorodova; V.P. Puzyrev; E.Y. Bragina; T.J. Hudson; C. Morin; D.L. Duffy; G.B. Marks; C.F. Robertson; G.W. Montgomery; B. Musk; Philip Thompson; N.G. Martin; A. James; P. Sleiman; E. Toskala; E. Rodriguez; R. Fölster-Holst; A. Franke; W. Lieb; C. Gieger; A. Heinzmann; E. Rietschel; T. Keil; S. Cichon; M.M. Nöthen; Craig Pennell; P.D. Sly; C.O. Schmidt; A. Matanovic; V. Schneider; M. Heinig; N. Hübner; Patrick Holt; S. Lau; M. Kabesch; S. Weidinger; H. Hakonarson; M.A.R. Ferreira; C. Laprise; M.B. Freidin; J. Genuneit; G.H. Koppelman; E. Melén; M.H. Dizier; A.J. Henderson; Y.A. Lee

doi:10.1038/ncomms9804

Meta-analysis identifies seven susceptibility loci involved in the atopic March

I. Marenholz, J. Esparza-Gordillo, F. Rüschendorf, A. Bauerfeind, D.P. Strachan, B.D. Spycher, H. Baurecht, P. Margaritte-Jeannin, A. Sääf, M. Kerkhof, M. Ege, Svetlana Baltic, M.C. Matheson, J. Li, S. Michel, Wei Ang, W. Mcardle, A. Arnold, G. Homuth, F. DemenaisE. Bouzigon, C. Söderhäll, G. Pershagen, J.C. De Jongste, D.S. Postma, C. Braun-Fahrländer, E. Horak, L.M. Ogorodova, V.P. Puzyrev, E.Y. Bragina, T.J. Hudson, C. Morin, D.L. Duffy, G.B. Marks, C.F. Robertson, G.W. Montgomery, B. Musk, Philip Thompson, N.G. Martin, A. James, P. Sleiman, E. Toskala, E. Rodriguez, R. Fölster-Holst, A. Franke, W. Lieb, C. Gieger, A. Heinzmann, E. Rietschel, T. Keil, S. Cichon, M.M. Nöthen, Craig Pennell, P.D. Sly, C.O. Schmidt, A. Matanovic, V. Schneider, M. Heinig, N. Hübner, Patrick Holt, S. Lau, M. Kabesch, S. Weidinger, H. Hakonarson, M.A.R. Ferreira, C. Laprise, M.B. Freidin, J. Genuneit, G.H. Koppelman, E. Melén, M.H. Dizier, A.J. Henderson, Y.A. Lee

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Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Eczema often precedes the development of asthma in a disease course called the a € atopic marcha €. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10 a'8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10 a'9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Original language	English
Pages (from-to)	Article 8804
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9804
Publication status	Published - 2015

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Marenholz, I., Esparza-Gordillo, J., Rüschendorf, F., Bauerfeind, A., Strachan, D. P., Spycher, B. D., Baurecht, H., Margaritte-Jeannin, P., Sääf, A., Kerkhof, M., Ege, M., Baltic, S., Matheson, M. C., Li, J., Michel, S., Ang, W., Mcardle, W., Arnold, A., Homuth, G., ... Lee, Y. A. (2015). Meta-analysis identifies seven susceptibility loci involved in the atopic March. Nature Communications, 6, Article 8804. https://doi.org/10.1038/ncomms9804

@article{6acc4e45250a4bfb9d170d63141de867,

title = "Meta-analysis identifies seven susceptibility loci involved in the atopic March",

abstract = "{\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved. Eczema often precedes the development of asthma in a disease course called the a € atopic marcha €. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10 a'8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10 a'9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.",

author = "I. Marenholz and J. Esparza-Gordillo and F. R{\"u}schendorf and A. Bauerfeind and D.P. Strachan and B.D. Spycher and H. Baurecht and P. Margaritte-Jeannin and A. S{\"a}{\"a}f and M. Kerkhof and M. Ege and Svetlana Baltic and M.C. Matheson and J. Li and S. Michel and Wei Ang and W. Mcardle and A. Arnold and G. Homuth and F. Demenais and E. Bouzigon and C. S{\"o}derh{\"a}ll and G. Pershagen and {De Jongste}, J.C. and D.S. Postma and C. Braun-Fahrl{\"a}nder and E. Horak and L.M. Ogorodova and V.P. Puzyrev and E.Y. Bragina and T.J. Hudson and C. Morin and D.L. Duffy and G.B. Marks and C.F. Robertson and G.W. Montgomery and B. Musk and Philip Thompson and N.G. Martin and A. James and P. Sleiman and E. Toskala and E. Rodriguez and R. F{\"o}lster-Holst and A. Franke and W. Lieb and C. Gieger and A. Heinzmann and E. Rietschel and T. Keil and S. Cichon and M.M. N{\"o}then and Craig Pennell and P.D. Sly and C.O. Schmidt and A. Matanovic and V. Schneider and M. Heinig and N. H{\"u}bner and Patrick Holt and S. Lau and M. Kabesch and S. Weidinger and H. Hakonarson and M.A.R. Ferreira and C. Laprise and M.B. Freidin and J. Genuneit and G.H. Koppelman and E. Mel{\'e}n and M.H. Dizier and A.J. Henderson and Y.A. Lee",

year = "2015",

doi = "10.1038/ncomms9804",

language = "English",

volume = "6",

pages = "Article 8804",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group - Macmillan Publishers",

}

Marenholz, I, Esparza-Gordillo, J, Rüschendorf, F, Bauerfeind, A, Strachan, DP, Spycher, BD, Baurecht, H, Margaritte-Jeannin, P, Sääf, A, Kerkhof, M, Ege, M, Baltic, S, Matheson, MC, Li, J, Michel, S, Ang, W, Mcardle, W, Arnold, A, Homuth, G, Demenais, F, Bouzigon, E, Söderhäll, C, Pershagen, G, De Jongste, JC, Postma, DS, Braun-Fahrländer, C, Horak, E, Ogorodova, LM, Puzyrev, VP, Bragina, EY, Hudson, TJ, Morin, C, Duffy, DL, Marks, GB, Robertson, CF, Montgomery, GW, Musk, B, Thompson, P, Martin, NG, James, A, Sleiman, P, Toskala, E, Rodriguez, E, Fölster-Holst, R, Franke, A, Lieb, W, Gieger, C, Heinzmann, A, Rietschel, E, Keil, T, Cichon, S, Nöthen, MM, Pennell, C, Sly, PD, Schmidt, CO, Matanovic, A, Schneider, V, Heinig, M, Hübner, N, Holt, P, Lau, S, Kabesch, M, Weidinger, S, Hakonarson, H, Ferreira, MAR, Laprise, C, Freidin, MB, Genuneit, J, Koppelman, GH, Melén, E, Dizier, MH, Henderson, AJ & Lee, YA 2015, 'Meta-analysis identifies seven susceptibility loci involved in the atopic March', Nature Communications, vol. 6, pp. Article 8804. https://doi.org/10.1038/ncomms9804

TY - JOUR

T1 - Meta-analysis identifies seven susceptibility loci involved in the atopic March

AU - Marenholz, I.

AU - Esparza-Gordillo, J.

AU - Rüschendorf, F.

AU - Bauerfeind, A.

AU - Strachan, D.P.

AU - Spycher, B.D.

AU - Baurecht, H.

AU - Margaritte-Jeannin, P.

AU - Sääf, A.

AU - Kerkhof, M.

AU - Ege, M.

AU - Baltic, Svetlana

AU - Matheson, M.C.

AU - Li, J.

AU - Michel, S.

AU - Ang, Wei

AU - Mcardle, W.

AU - Arnold, A.

AU - Homuth, G.

AU - Demenais, F.

AU - Bouzigon, E.

AU - Söderhäll, C.

AU - Pershagen, G.

AU - De Jongste, J.C.

AU - Postma, D.S.

AU - Braun-Fahrländer, C.

AU - Horak, E.

AU - Ogorodova, L.M.

AU - Puzyrev, V.P.

AU - Bragina, E.Y.

AU - Hudson, T.J.

AU - Morin, C.

AU - Duffy, D.L.

AU - Marks, G.B.

AU - Robertson, C.F.

AU - Montgomery, G.W.

AU - Musk, B.

AU - Thompson, Philip

AU - Martin, N.G.

AU - James, A.

AU - Sleiman, P.

AU - Toskala, E.

AU - Rodriguez, E.

AU - Fölster-Holst, R.

AU - Franke, A.

AU - Lieb, W.

AU - Gieger, C.

AU - Heinzmann, A.

AU - Rietschel, E.

AU - Keil, T.

AU - Cichon, S.

AU - Nöthen, M.M.

AU - Pennell, Craig

AU - Sly, P.D.

AU - Schmidt, C.O.

AU - Matanovic, A.

AU - Schneider, V.

AU - Heinig, M.

AU - Hübner, N.

AU - Holt, Patrick

AU - Lau, S.

AU - Kabesch, M.

AU - Weidinger, S.

AU - Hakonarson, H.

AU - Ferreira, M.A.R.

AU - Laprise, C.

AU - Freidin, M.B.

AU - Genuneit, J.

AU - Koppelman, G.H.

AU - Melén, E.

AU - Dizier, M.H.

AU - Henderson, A.J.

AU - Lee, Y.A.

PY - 2015

Y1 - 2015

N2 - © 2015 Macmillan Publishers Limited. All rights reserved. Eczema often precedes the development of asthma in a disease course called the a € atopic marcha €. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10 a'8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10 a'9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

AB - © 2015 Macmillan Publishers Limited. All rights reserved. Eczema often precedes the development of asthma in a disease course called the a € atopic marcha €. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10 a'8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10 a'9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

U2 - 10.1038/ncomms9804

DO - 10.1038/ncomms9804

M3 - Article

C2 - 26542096

VL - 6

SP - Article 8804

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -

Meta-analysis identifies seven susceptibility loci involved in the atopic March

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