Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Lavinia Paternoster (Lead / Corresponding author), Marie Standl, Johannes Waage, Hansjörg Baurecht, Melanie Hotze, David P. Strachan, John A. Curtin, Klaus Bønnelykke, Chao Tian, Atsushi Takahashi, Jorge Esparza-Gordillo, Alexessander Couto Alves, Jacob P. Thyssen, Herman T. Den Dekker, Manuel A. Ferreira, Elisabeth Altmaier, Patrick M A Sleiman, Feng Li Xiao, Juan R. Gonzalez, Ingo MarenholzBirgit Kalb, Maria Pino-Yanes, Cheng Jian Xu, Lisbeth Carstensen, Maria M. Groen-Blokhuis, Cristina Venturini, Craig E. Pennell, Sheila J. Barton, Albert M. Levin, Ivan Curjuric, Mariona Bustamante, Eskil Kreiner-Møller, Gabrielle A. Lockett, Jonas Bacelis, Supinda Bunyavanich, Rachel A. Myers, Anja Matanovic, Ashish Kumar, Joyce Y. Tung, Tomomitsu Hirota, Michiaki Kubo, Wendy L. McArdle, A. John Henderson, John P. Kemp, Jie Zheng, George Davey Smith, Franz Rüschendorf, Anja Bauerfeind, Min Ae Lee-Kirsch, Andreas Arnold, Georg Homuth, Carsten O. Schmidt, Elisabeth Mangold, Sven Cichon, Thomas Keil, Elke Rodríguez, Annette Peters, Andre Franke, Wolfgang Lieb, Natalija Novak, Regina Fölster-Holst, Momoko Horikoshi, Juha Pekkanen, Sylvain Sebert, Lise L. Husemoen, Niels Grarup, Johan C. De Jongste, Fernando Rivadeneira, Albert Hofman, Vincent W V Jaddoe, Suzanne G M A Pasmans, Niels J. Elbert, André G. Uitterlinden, Guy B. Marks, Philip J. Thompson, Melanie C. Matheson, Colin F. Robertson, Janina S. Ried, Jin Li, Xian Bo Zuo, Xiao Dong Zheng, Xian Yong Yin, Liang Dan Sun, Maeve A. McAleer, Grainne M. O'Regan, Caoimhe M R Fahy, Linda E. Campbell, Milan Macek, Michael Kurek, Donglei Hu, Celeste Eng, Dirkje S. Postma, Bjarke Feenstra, Frank Geller, Jouke Jan Hottenga, Christel M. Middeldorp, Pirro Hysi, Veronique Bataille, Tim Spector, Carla M T Tiesler, Elisabeth Thiering, Badri Pahukasahasram, James J. Yang, Medea Imboden, Scott Huntsman, Natàlia Vilor-Tejedor, Caroline L. Relton, Ronny Myhre, Wenche Nystad, Adnan Custovic, Scott T. Weiss, Deborah A. Meyers, Cilla Söderhäll, Erik Melén, Carole Ober, Benjamin A. Raby, Angela Simpson, Bo Jacobsson, John W. Holloway, Hans Bisgaard, Jordi Sunyer, Nicole M. Probst-Hensch, L. Keoki Williams, Keith M. Godfrey, Carol A. Wang, Dorret I. Boomsma, Mads Melbye, Gerard H. Koppelman, Deborah Jarvis, W. H Irwin McLean, Alan D. Irvine, Xue Jun Zhang, Hakon Hakonarson, Christian Gieger, Esteban G. Burchard, Nicholas G. Martin, Liesbeth Duijts, Allan Linneberg, Marjo Riitta Jarvelin, Markus M. Nöthen, Susanne Lau, Norbert Hübner, Young Ae Lee, Mayumi Tamari, David A. Hinds, Daniel Glass, Sara J. Brown, Joachim Heinrich, David M. Evans, Stephan Weidinger

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Abstract

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

Original languageEnglish
Pages (from-to)1449-1456
Number of pages8
JournalNature Genetics
Volume47
Issue number12
Early online date19 Oct 2015
DOIs
Publication statusPublished - Dec 2015

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Paternoster, L., Standl, M., Waage, J., Baurecht, H., Hotze, M., Strachan, D. P., Curtin, J. A., Bønnelykke, K., Tian, C., Takahashi, A., Esparza-Gordillo, J., Alves, A. C., Thyssen, J. P., Den Dekker, H. T., Ferreira, M. A., Altmaier, E., Sleiman, P. M. A., Xiao, F. L., Gonzalez, J. R., ... Weidinger, S. (2015). Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nature Genetics, 47(12), 1449-1456. https://doi.org/10.1038/ng.3424