TY - JOUR
T1 - European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
AU - Budu-Aggrey, Ashley
AU - Kilanowski, Anna
AU - Sobczyk, Maria K.
AU - Shringarpure, Suyash S.
AU - Mitchell, Ruth
AU - Reis, Kadri
AU - Reigo, Anu
AU - Mägi, Reedik
AU - Nelis, Mari
AU - Tanaka, Nao
AU - Brumpton, Ben M.
AU - Thomas, Laurent F.
AU - Sole-Navais, Pol
AU - Flatley, Christopher
AU - Espuela-Ortiz, Antonio
AU - Herrera-Luis, Esther
AU - Lominchar, Jesus V.T.
AU - Bork-Jensen, Jette
AU - Marenholz, Ingo
AU - Arnau-Soler, Aleix
AU - Jeong, Ayoung
AU - Fawcett, Katherine A.
AU - Baurecht, Hansjorg
AU - Rodriguez, Elke
AU - Alves, Alexessander Couto
AU - Kumar, Ashish
AU - Sleiman, Patrick M.
AU - Chang, Xiao
AU - Medina-Gomez, Carolina
AU - Hu, Chen
AU - Xu, Cheng jian
AU - Qi, Cancan
AU - El-Heis, Sarah
AU - Titcombe, Philip
AU - Antoun, Elie
AU - Fadista, João
AU - Wang, Carol A.
AU - Thiering, Elisabeth
AU - Wu, Baojun
AU - Kress, Sara
AU - Kothalawala, Dilini M.
AU - Kadalayil, Latha
AU - Duan, Jiasong
AU - Zhang, Hongmei
AU - Hadebe, Sabelo
AU - Hoffmann, Thomas
AU - Jorgenson, Eric
AU - Curtin, John
AU - Simpson, Angela
AU - Murray, Clare
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/10/4
Y1 - 2023/10/4
N2 - 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.
AB - 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.
KW - Humans
KW - Genome-Wide Association Study
KW - Dermatitis, Atopic/genetics
KW - Genetic Predisposition to Disease/genetics
KW - Hispanic or Latino/genetics
KW - Black People
KW - Polymorphism, Single Nucleotide
UR - http://www.scopus.com/inward/record.url?scp=85173731134&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/a9167e63-013a-3d81-840a-c60b9f37adf5/
U2 - 10.1038/s41467-023-41180-2
DO - 10.1038/s41467-023-41180-2
M3 - Article
C2 - 37794016
AN - SCOPUS:85173731134
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6172
ER -