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

Ashley Budu-Aggrey; Anna Kilanowski; Maria K. Sobczyk; Suyash S. Shringarpure; Ruth Mitchell; Kadri Reis; Anu Reigo; Reedik Mägi; Mari Nelis; Nao Tanaka; Ben M. Brumpton; Laurent F. Thomas; Pol Sole-Navais; Christopher Flatley; Antonio Espuela-Ortiz; Esther Herrera-Luis; Jesus V.T. Lominchar; Jette Bork-Jensen; Ingo Marenholz; Aleix Arnau-Soler; Ayoung Jeong; Katherine A. Fawcett; Hansjorg Baurecht; Elke Rodriguez; Alexessander Couto Alves; Ashish Kumar; Patrick M. Sleiman; Xiao Chang; Carolina Medina-Gomez; Chen Hu; Cheng jian Xu; Cancan Qi; Sarah El-Heis; Philip Titcombe; Elie Antoun; João Fadista; Carol A. Wang; Elisabeth Thiering; Baojun Wu; Sara Kress; Dilini M. Kothalawala; Latha Kadalayil; Jiasong Duan; Hongmei Zhang; Sabelo Hadebe; Thomas Hoffmann; Eric Jorgenson; Hélène Choquet; Neil Risch; Pål Njølstad; Ole A. Andreassen; Stefan Johansson; Catarina Almqvist; Tong Gong; Vilhelmina Ullemar; Robert Karlsson; Patrik K.E. Magnusson; Agnieszka Szwajda; Esteban G. Burchard; Jacob P. Thyssen; Torben Hansen; Line L. Kårhus; Thomas M. Dantoft; Alexander C.S.N. Jeanrenaud; Ahla Ghauri; Andreas Arnold; Georg Homuth; Susanne Lau; Markus M. Nöthen; Norbert Hübner; Medea Imboden; Alessia Visconti; Mario Falchi; Veronique Bataille; Pirro Hysi; Natalia Ballardini; Dorret I. Boomsma; Jouke J. Hottenga; Martina Müller-Nurasyid; Tarunveer S. Ahluwalia; Jakob Stokholm; Bo Chawes; Ann Marie M. Schoos; Ana Esplugues; Mariona Bustamante; Benjamin Raby; Syed Arshad; Chris German; Tõnu Esko; Lili A. Milani; Andres Metspalu; Chikashi Terao; Katrina Abuabara; Mari Løset; Kristian Hveem; Bo Jacobsson; Maria Pino-Yanes; David P. Strachan; Niels Grarup; Allan Linneberg; Young Ae Lee; Nicole Probst-Hensch; Stephan Weidinger; Marjo Riitta Jarvelin; Erik Melén; Hakon Hakonarson; Alan D. Irvine; Deborah Jarvis; Tamar Nijsten; Liesbeth Duijts; Judith M. Vonk; Gerard H. Koppelmann; Keith M. Godfrey; Sheila J. Barton; Bjarke Feenstra; Craig E. Pennell; Peter D. Sly; Patrick G. Holt; L. Keoki Williams; Hans Bisgaard; Klaus Bønnelykke; John Curtin; Angela Simpson; Clare Murray; Tamara Schikowski; Supinda Bunyavanich; Scott T. Weiss; John W. Holloway; Josine L. Min; Sara J. Brown; Marie Standl; Lavinia Paternoster

doi:10.1038/s41467-023-41180-2

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

Ashley Budu-Aggrey
, Anna Kilanowski
, Maria K. Sobczyk
, Suyash S. Shringarpure
, Ruth Mitchell
, Kadri Reis
, Anu Reigo
, Reedik Mägi
, Mari Nelis
, Nao Tanaka
, Ben M. Brumpton
, Laurent F. Thomas
, Pol Sole-Navais
, Christopher Flatley
, Antonio Espuela-Ortiz
, Esther Herrera-Luis
, Jesus V.T. Lominchar
, Jette Bork-Jensen
, Ingo Marenholz
, Aleix Arnau-Soler

Ayoung Jeong, Katherine A. Fawcett, Hansjorg Baurecht, Elke Rodriguez, Alexessander Couto Alves, Ashish Kumar, Patrick M. Sleiman, Xiao Chang, Carolina Medina-Gomez, Chen Hu, Cheng jian Xu, Cancan Qi, Sarah El-Heis, Philip Titcombe, Elie Antoun, João Fadista, Carol A. Wang, Elisabeth Thiering, Baojun Wu, Sara Kress, Dilini M. Kothalawala, Latha Kadalayil, Jiasong Duan, Hongmei Zhang, Sabelo Hadebe, Thomas Hoffmann, Eric Jorgenson, Hélène Choquet, Neil Risch, Pål Njølstad, Ole A. Andreassen, Stefan Johansson, Catarina Almqvist, Tong Gong, Vilhelmina Ullemar, Robert Karlsson, Patrik K.E. Magnusson, Agnieszka Szwajda, Esteban G. Burchard, Jacob P. Thyssen, Torben Hansen, Line L. Kårhus, Thomas M. Dantoft, Alexander C.S.N. Jeanrenaud, Ahla Ghauri, Andreas Arnold, Georg Homuth, Susanne Lau, Markus M. Nöthen, Norbert Hübner, Medea Imboden, Alessia Visconti, Mario Falchi, Veronique Bataille, Pirro Hysi, Natalia Ballardini, Dorret I. Boomsma, Jouke J. Hottenga, Martina Müller-Nurasyid, Tarunveer S. Ahluwalia, Jakob Stokholm, Bo Chawes, Ann Marie M. Schoos, Ana Esplugues, Mariona Bustamante, Benjamin Raby, Syed Arshad, Chris German, Tõnu Esko, Lili A. Milani, Andres Metspalu, Chikashi Terao, Katrina Abuabara, Mari Løset, Kristian Hveem, Bo Jacobsson, Maria Pino-Yanes, David P. Strachan, Niels Grarup, Allan Linneberg, Young Ae Lee, Nicole Probst-Hensch, Stephan Weidinger, Marjo Riitta Jarvelin, Erik Melén, Hakon Hakonarson, Alan D. Irvine, Deborah Jarvis, Tamar Nijsten, Liesbeth Duijts, Judith M. Vonk, Gerard H. Koppelmann, Keith M. Godfrey, Sheila J. Barton, Bjarke Feenstra, Craig E. Pennell, Peter D. Sly, Patrick G. Holt, L. Keoki Williams, Hans Bisgaard, Klaus Bønnelykke, John Curtin, Angela Simpson, Clare Murray, Tamara Schikowski, Supinda Bunyavanich, Scott T. Weiss, John W. Holloway, Josine L. Min, Sara J. Brown, Marie Standl, Lavinia Paternoster^*

^*Corresponding author for this work

University of Bristol
Helmholtz Zentrum München - German Research Center for Environmental Health
Ludwig Maximilian University of Munich
23andMe Inc.
University of Tartu
University of Tartu
RIKEN
Institute of Science Tokyo
Norwegian University of Science and Technology
University of Gothenburg
University of La Laguna
University of Copenhagen
Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Charité – Universitätsmedizin Berlin
Swiss Tropical and Public Health Institute
University of Basel
University of Leicester
University of Regensburg
University Hospital of Schleswig-Holstein
University of Surrey
Karolinska Institutet
Children's Hospital of Philadelphia
University of Pennsylvania
Rhythm Pharmaceuticals
Erasmus University Rotterdam
University of Groningen
Helmholtz Centre for Infection Research
TWINCORE-Centre for Experimental and Clinical Infection Research
MRC Lifecourse Epidemiology Unit
University of Southampton
Statens Serum Institut
Lund University
University of Helsinki
University of Newcastle
Hunter Medical Research Institute, Australia
Henry Ford Health System
Leibniz Research Institute for Environmental Medicine
NIHR Southampton Biomedical Research Centre
University of Memphis
University of Cape Town
University of California at San Francisco
Regeneron Pharmaceuticals, Inc.
Kaiser Permanente
University of Bergen
University of Oslo
University of Greifswald
University of Bonn
King's College London
West Hertfordshire Hospitals NHS Trust
Vrije Universiteit Amsterdam
Vrije Universiteit (VU)
Johannes Gutenberg University Mainz
Novo Nordisk Foundation
Slagelse Hospital
University of Valencia
Biomedical Research Networking Center in Epidemiology and Public Health (CiberESP)
Barcelona Institute for Global Health
Pompeu Fabra University
Brigham and Women’s Hospital
David Hide Asthma and Allergy Research Centre
Shizuoka General Hospital
University of Shizuoka
Norwegian Institute of Public Health
Centro de Investigacion Biomedica en Red Enfermedades Respiratorias (CIBERES)
St. George's University of London
Imperial College London
University of Oulu
University of Iceland
Trinity College Dublin
University of Queensland
Telethon Kids Institute
University of Manchester
Icahn School of Medicine at Mount Sinai
University of Edinburgh
German Center for Lung Research (DZL)

Research output: Contribution to journal › Article › peer-review

81 Citations (Scopus)

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.

Original language	English
Article number	6172
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-41180-2
Publication status	Published - 4 Oct 2023
Externally published	Yes

Keywords

Children
Filaggrin
Gene-expression
Gwas
Pathways
Regression
Reveals
Susceptibility loci
Transcriptome
Variants

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10.1038/s41467-023-41180-2

Cite this

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., ... Paternoster, L. (2023). European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation. Nature Communications, 14(1), Article 6172. https://doi.org/10.1038/s41467-023-41180-2

@article{78aeeb5a12f544fb9a43b640d7d12350,

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

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.",

keywords = "Children, Filaggrin, Gene-expression, Gwas, Pathways, Regression, Reveals, Susceptibility loci, Transcriptome, Variants",

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

note = "Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",

year = "2023",

month = oct,

day = "4",

doi = "10.1038/s41467-023-41180-2",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

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Budu-Aggrey, A, Kilanowski, A, Sobczyk, MK, Shringarpure, SS, Mitchell, R, Reis, K, Reigo, A, Mägi, R, Nelis, M, Tanaka, N, Brumpton, BM, Thomas, LF, Sole-Navais, P, Flatley, C, Espuela-Ortiz, A, Herrera-Luis, E, Lominchar, JVT, Bork-Jensen, J, Marenholz, I, Arnau-Soler, A, Jeong, A, Fawcett, KA, Baurecht, H, Rodriguez, E, Alves, AC, Kumar, A, Sleiman, PM, Chang, X, Medina-Gomez, C, Hu, C, Xu, CJ, Qi, C, El-Heis, S, Titcombe, P, Antoun, E, Fadista, J, Wang, CA, Thiering, E, Wu, B, Kress, S, Kothalawala, DM, Kadalayil, L, Duan, J, Zhang, H, Hadebe, S, Hoffmann, T, Jorgenson, E, Choquet, H, Risch, N, Njølstad, P, Andreassen, OA, Johansson, S, Almqvist, C, Gong, T, Ullemar, V, Karlsson, R, Magnusson, PKE, Szwajda, A, Burchard, EG, Thyssen, JP, Hansen, T, Kårhus, LL, Dantoft, TM, Jeanrenaud, ACSN, Ghauri, A, Arnold, A, Homuth, G, Lau, S, Nöthen, MM, Hübner, N, Imboden, M, Visconti, A, Falchi, M, Bataille, V, Hysi, P, Ballardini, N, Boomsma, DI, Hottenga, JJ, Müller-Nurasyid, M, Ahluwalia, TS, Stokholm, J, Chawes, B, Schoos, AMM, Esplugues, A, Bustamante, M, Raby, B, Arshad, S, German, C, Esko, T, Milani, LA, Metspalu, A, Terao, C, Abuabara, K, Løset, M, Hveem, K, Jacobsson, B, Pino-Yanes, M, Strachan, DP, Grarup, N, Linneberg, A, Lee, YA, Probst-Hensch, N, Weidinger, S, Jarvelin, MR, Melén, E, Hakonarson, H, Irvine, AD, Jarvis, D, Nijsten, T, Duijts, L, Vonk, JM, Koppelmann, GH, Godfrey, KM, Barton, SJ, Feenstra, B, Pennell, CE, Sly, PD, Holt, PG, Williams, LK, Bisgaard, H, Bønnelykke, K, Curtin, J, Simpson, A, Murray, C, Schikowski, T, Bunyavanich, S, Weiss, ST, Holloway, JW, Min, JL, Brown, SJ, Standl, M & Paternoster, L 2023, 'European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation', Nature Communications, vol. 14, no. 1, 6172. https://doi.org/10.1038/s41467-023-41180-2

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 - Choquet, Hélène

AU - Risch, Neil

AU - Njølstad, Pål

AU - Andreassen, Ole A.

AU - Johansson, Stefan

AU - Almqvist, Catarina

AU - Gong, Tong

AU - Ullemar, Vilhelmina

AU - Karlsson, Robert

AU - Magnusson, Patrik K.E.

AU - Szwajda, Agnieszka

AU - Burchard, Esteban G.

AU - Thyssen, Jacob P.

AU - Hansen, Torben

AU - Kårhus, Line L.

AU - Dantoft, Thomas M.

AU - Jeanrenaud, Alexander C.S.N.

AU - Ghauri, Ahla

AU - Arnold, Andreas

AU - Homuth, Georg

AU - Lau, Susanne

AU - Nöthen, Markus M.

AU - Hübner, Norbert

AU - Imboden, Medea

AU - Visconti, Alessia

AU - Falchi, Mario

AU - Bataille, Veronique

AU - Hysi, Pirro

AU - Ballardini, Natalia

AU - Boomsma, Dorret I.

AU - Hottenga, Jouke J.

AU - Müller-Nurasyid, Martina

AU - Ahluwalia, Tarunveer S.

AU - Stokholm, Jakob

AU - Chawes, Bo

AU - Schoos, Ann Marie M.

AU - Esplugues, Ana

AU - Bustamante, Mariona

AU - Raby, Benjamin

AU - Arshad, Syed

AU - German, Chris

AU - Esko, Tõnu

AU - Milani, Lili A.

AU - Metspalu, Andres

AU - Terao, Chikashi

AU - Abuabara, Katrina

AU - Løset, Mari

AU - Hveem, Kristian

AU - Jacobsson, Bo

AU - Pino-Yanes, Maria

AU - Strachan, David P.

AU - Grarup, Niels

AU - Linneberg, Allan

AU - Lee, Young Ae

AU - Probst-Hensch, Nicole

AU - Weidinger, Stephan

AU - Jarvelin, Marjo Riitta

AU - Melén, Erik

AU - Hakonarson, Hakon

AU - Irvine, Alan D.

AU - Jarvis, Deborah

AU - Nijsten, Tamar

AU - Duijts, Liesbeth

AU - Vonk, Judith M.

AU - Koppelmann, Gerard H.

AU - Godfrey, Keith M.

AU - Barton, Sheila J.

AU - Feenstra, Bjarke

AU - Pennell, Craig E.

AU - Sly, Peter D.

AU - Holt, Patrick G.

AU - Williams, L. Keoki

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

AU - Curtin, John

AU - Simpson, Angela

AU - Murray, Clare

AU - Schikowski, Tamara

AU - Bunyavanich, Supinda

AU - Weiss, Scott T.

AU - Holloway, John W.

AU - Min, Josine L.

AU - Brown, Sara J.

AU - Standl, Marie

AU - Paternoster, Lavinia

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 - Children

KW - Filaggrin

KW - Gene-expression

KW - Gwas

KW - Pathways

KW - Regression

KW - Reveals

KW - Susceptibility loci

KW - Transcriptome

KW - Variants

UR - https://www.scopus.com/pages/publications/85173731134

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 -

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

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Keywords

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