European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Budu-Aggrey, A.; Kilanowski, A.; Sobczyk, M. K.; Shringarpure, S. S.; Mitchell, R.; Reis, K.; Reigo, A.; Magi, R.; Nelis, M.; Tanaka, N.; Brumpton, B. M.; Thomas, L. F.; Sole-Navais, P.; Flatley, C.; Espuela-Ortiz, A.; Herrera-Luis, E.; Lominchar, J. V. T.; Bork-Jensen, J.; Marenholz, I.; Arnau-Soler, A.; Jeong, A.; Fawcett, K. A.; Baurecht, H.; Rodriguez, E.; Alves, A. C.; Kumar, A.; Sleiman, P. M.; Chang, X.; Medina-Gomez, C.; Hu, C.; C. -J., Xu; Qi, C.; El-Heis, S.; Titcombe, P.; Antoun, E.; Fadista, J.; Wang, C. A.; Thiering, E.; Wu, B.; Kress, S.; Kothalawala, D. M.; Kadalayil, L.; Duan, J.; Zhang, H.; Hadebe, S.; Hoffmann, T.; Jorgenson, E.; Choquet, H.; Risch, N.; Njolstad, P.; Andreassen, O. A.; Johansson, S.; Almqvist, C.; Gong, T.; Ullemar, V.; Karlsson, R.; Magnusson, P. K. E.; Szwajda, A.; Burchard, E. G.; Thyssen, J. P.; Hansen, T.; Karhus, L. L.; Dantoft, T. M.; Jeanrenaud, A. C. S. N.; Ghauri, A.; Arnold, A.; Homuth, G.; Lau, S.; Nothen, M. M.; Hubner, N.; Imboden, M.; Visconti, A.; Falchi, M.; Bataille, V.; Hysi, P.; Ballardini, N.; Boomsma, D. I.; Hottenga, J. J.; Muller-Nurasyid, M.; Ahluwalia, T. S.; Stokholm, J.; Chawes, B.; Schoos, A. -M. M.; Esplugues, A.; Bustamante, M.; Raby, B.; Arshad, S.; German, C.; Esko, T.; Milani, L. A.; Metspalu, A.; Terao, C.; Abuabara, K.; Loset, M.; Hveem, K.; Jacobsson, B.; Pino-Yanes, M.; Strachan, D. P.; Grarup, N.; Linneberg, A.; Lee, Y. -A.; Probst-Hensch, N.; Weidinger, S.; Jarvelin, M. -R.; Melen, E.; Hakonarson, H.; Irvine, A. D.; Jarvis, D.; Nijsten, T.; Duijts, L.; Vonk, J. M.; Koppelmann, G. H.; Godfrey, K. M.; Barton, S. J.; Feenstra, B.; Pennell, C. E.; Sly, P. D.; Holt, P. G.; Williams, L. K.; Bisgaard, H.; Bonnelykke, K.; Curtin, J.; Simpson, A.; Murray, C.; Schikowski, T.; Bunyavanich, S.; Weiss, S. T.; Holloway, J. W.; Min, J. L.; Brown, S. J.; Standl, M.; Paternoster, L.

doi:10.1038/s41467-023-41180-2

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.