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

Authors :
Budu-Aggrey, Ashley
Kilanowski, Anna
Sobczyk, Maria K.
Shringarpure, Suyash S.
Mitchell, Ruth
Reis, Kadri
Reigo, Anu
Mägi, Reedik
Nelis, Mari
Tanaka, Nao
Brumpton, Ben M.
Thomas, Laurent F.
Sole-Navais, Pol
Flatley, Christopher
Espuela-Ortiz, Antonio
Herrera-Luis, Esther
Lominchar, Jesus V.T.
Bork-Jensen, Jette
Marenholz, Ingo
Arnau-Soler, Aleix
Jeong, Ayoung
Fawcett, Katherine A.
Baurecht, Hansjorg
Rodriguez, Elke
Alves, Alexessander Couto
Kumar, Ashish
Sleiman, Patrick M.
Chang, Xiao
Medina-Gomez, Carolina
Hu, Chen
Xu, Cheng jian
Qi, Cancan
El-Heis, Sarah
Titcombe, Philip
Antoun, Elie
Fadista, João
Wang, Carol A.
Thiering, Elisabeth
Wu, Baojun
Kress, Sara
Kothalawala, Dilini M.
Kadalayil, Latha
Duan, Jiasong
Zhang, Hongmei
Hadebe, Sabelo
Hoffmann, Thomas
Jorgenson, Eric
Choquet, Hélène
Risch, Neil
Njølstad, Pål
Andreassen, Ole A.
Johansson, Stefan
Almqvist, Catarina
Gong, Tong
Ullemar, Vilhelmina
Karlsson, Robert
Magnusson, Patrik K.E.
Szwajda, Agnieszka
Burchard, Esteban G.
Thyssen, Jacob P.
Hansen, Torben
Kårhus, Line L.
Dantoft, Thomas M.
Jeanrenaud, Alexander C.S.N.
Ghauri, Ahla
Arnold, Andreas
Homuth, Georg
Lau, Susanne
Nöthen, Markus M.
Hübner, Norbert
Imboden, Medea
Visconti, Alessia
Falchi, Mario
Bataille, Veronique
Hysi, Pirro
Ballardini, Natalia
Boomsma, Dorret I.
Hottenga, Jouke J.
Müller-Nurasyid, Martina
Ahluwalia, Tarunveer S.
Stokholm, Jakob
Chawes, Bo
Schoos, Ann Marie M.
Esplugues, Ana
Bustamante, Mariona
Raby, Benjamin
Arshad, Syed
German, Chris
Esko, Tõnu
Milani, Lili A.
Metspalu, Andres
Terao, Chikashi
Abuabara, Katrina
Løset, Mari
Hveem, Kristian
Jacobsson, Bo
Pino-Yanes, Maria
Strachan, David P.
Grarup, Niels
Linneberg, Allan
Lee, Young Ae
Probst-Hensch, Nicole
Weidinger, Stephan
Jarvelin, Marjo Riitta
Melén, Erik
Hakonarson, Hakon
Irvine, Alan D.
Jarvis, Deborah
Nijsten, Tamar
Duijts, Liesbeth
Vonk, Judith M.
Koppelmann, Gerard H.
Godfrey, Keith M.
Barton, Sheila J.
Feenstra, Bjarke
Pennell, Craig E.
Sly, Peter D.
Holt, Patrick G.
Williams, L. Keoki
Bisgaard, Hans
Bønnelykke, Klaus
Curtin, John
Simpson, Angela
Murray, Clare
Schikowski, Tamara
Bunyavanich, Supinda
Weiss, Scott T.
Holloway, John W.
Min, Josine L.
Brown, Sara J.
Standl, Marie
Paternoster, Lavinia
Budu-Aggrey, Ashley
Kilanowski, Anna
Sobczyk, Maria K.
Shringarpure, Suyash S.
Mitchell, Ruth
Reis, Kadri
Reigo, Anu
Mägi, Reedik
Nelis, Mari
Tanaka, Nao
Brumpton, Ben M.
Thomas, Laurent F.
Sole-Navais, Pol
Flatley, Christopher
Espuela-Ortiz, Antonio
Herrera-Luis, Esther
Lominchar, Jesus V.T.
Bork-Jensen, Jette
Marenholz, Ingo
Arnau-Soler, Aleix
Jeong, Ayoung
Fawcett, Katherine A.
Baurecht, Hansjorg
Rodriguez, Elke
Alves, Alexessander Couto
Kumar, Ashish
Sleiman, Patrick M.
Chang, Xiao
Medina-Gomez, Carolina
Hu, Chen
Xu, Cheng jian
Qi, Cancan
El-Heis, Sarah
Titcombe, Philip
Antoun, Elie
Fadista, João
Wang, Carol A.
Thiering, Elisabeth
Wu, Baojun
Kress, Sara
Kothalawala, Dilini M.
Kadalayil, Latha
Duan, Jiasong
Zhang, Hongmei
Hadebe, Sabelo
Hoffmann, Thomas
Jorgenson, Eric
Choquet, Hélène
Risch, Neil
Njølstad, Pål
Andreassen, Ole A.
Johansson, Stefan
Almqvist, Catarina
Gong, Tong
Ullemar, Vilhelmina
Karlsson, Robert
Magnusson, Patrik K.E.
Szwajda, Agnieszka
Burchard, Esteban G.
Thyssen, Jacob P.
Hansen, Torben
Kårhus, Line L.
Dantoft, Thomas M.
Jeanrenaud, Alexander C.S.N.
Ghauri, Ahla
Arnold, Andreas
Homuth, Georg
Lau, Susanne
Nöthen, Markus M.
Hübner, Norbert
Imboden, Medea
Visconti, Alessia
Falchi, Mario
Bataille, Veronique
Hysi, Pirro
Ballardini, Natalia
Boomsma, Dorret I.
Hottenga, Jouke J.
Müller-Nurasyid, Martina
Ahluwalia, Tarunveer S.
Stokholm, Jakob
Chawes, Bo
Schoos, Ann Marie M.
Esplugues, Ana
Bustamante, Mariona
Raby, Benjamin
Arshad, Syed
German, Chris
Esko, Tõnu
Milani, Lili A.
Metspalu, Andres
Terao, Chikashi
Abuabara, Katrina
Løset, Mari
Hveem, Kristian
Jacobsson, Bo
Pino-Yanes, Maria
Strachan, David P.
Grarup, Niels
Linneberg, Allan
Lee, Young Ae
Probst-Hensch, Nicole
Weidinger, Stephan
Jarvelin, Marjo Riitta
Melén, Erik
Hakonarson, Hakon
Irvine, Alan D.
Jarvis, Deborah
Nijsten, Tamar
Duijts, Liesbeth
Vonk, Judith M.
Koppelmann, Gerard H.
Godfrey, Keith M.
Barton, Sheila J.
Feenstra, Bjarke
Pennell, Craig E.
Sly, Peter D.
Holt, Patrick G.
Williams, L. Keoki
Bisgaard, Hans
Bønnelykke, Klaus
Curtin, John
Simpson, Angela
Murray, Clare
Schikowski, Tamara
Bunyavanich, Supinda
Weiss, Scott T.
Holloway, John W.
Min, Josine L.
Brown, Sara J.
Standl, Marie
Paternoster, Lavinia
Source :
Budu-Aggrey , A , Kilanowski , A , Sobczyk , M K , Shringarpure , S S , Mitchell , R , Reis , K , Reigo , A , Mägi , 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 , Xu , C J , 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 , Njølstad , 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 , Kårhus , L L , Dantoft , T M , Jeanrenaud , A C S N , Ghauri , A , Arnold , A , Homuth , G , Lau , S , Nöthen , M M , Hübner , N , Imboden , M , Visconti , A , Falchi , M , Bataille , V , Hysi , P , Ballardini , N , Boomsma , D I , Hottenga , J J , Müller-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 , Løset , 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 , Melén , 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 , Bønnelykke , 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 2023 , ' European and multi-ancestry genome-wi
Publication Year :
2023

Abstract

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.

Details

Database :
OAIster
Journal :
Budu-Aggrey , A , Kilanowski , A , Sobczyk , M K , Shringarpure , S S , Mitchell , R , Reis , K , Reigo , A , Mägi , 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 , Xu , C J , 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 , Njølstad , 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 , Kårhus , L L , Dantoft , T M , Jeanrenaud , A C S N , Ghauri , A , Arnold , A , Homuth , G , Lau , S , Nöthen , M M , Hübner , N , Imboden , M , Visconti , A , Falchi , M , Bataille , V , Hysi , P , Ballardini , N , Boomsma , D I , Hottenga , J J , Müller-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 , Løset , 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 , Melén , 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 , Bønnelykke , 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 2023 , ' European and multi-ancestry genome-wi
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1439550370
Document Type :
Electronic Resource