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

by Espuela-Ortiz, Antonio , Kadalayil, Latha , Paternoster, Lavinia , Shringarpure, Suyash S. , Sobczyk, Maria K. , Choquet, Hélène , Titcombe, Philip , Terao, Chikashi , Kårhus, Line L. , Ahluwalia, Tarunveer S. , Sleiman, Patrick M. , Johansson, Stefan , Hveem, Kristian , Probst-Hensch, Nicole , Ullemar, Vilhelmina , Sly, Peter D. , Mitchell, Ruth , Almqvist, Catarina , Hoffmann, Thomas , Boomsma, Dorret I. , Medina-Gomez, Carolina , Esko, Tõnu , Standl, Marie , Nelis, Mari , Bork-Jensen, Jette , Vonk, Judith M. , Magnusson, Patrik K. E. , Duan, Jiasong , Mägi, Reedik , Grarup, Niels , Arnau-Soler, Aleix , Njølstad, Pål , Hu, Chen , Lau, Susanne , Feenstra, Bjarke , Brown, Sara J. , Simpson, Angela , Hakonarson, Hakon , Linneberg, Allan , Brumpton, Ben M. , German, Chris , Pino-Yanes, Maria , Burchard, Esteban G. , Kumar, Ashish , Thomas, Laurent F. , Wang, Carol A. , Hadebe, Sabelo , Flatley, Christopher , Jeong, Ayoung , Ballardini, Natalia , Qi, Cancan , Gong, Tong , Murray, Clare , Hottenga, Jouke J. , Müller-Nurasyid, Martina , Jarvis, Deborah , Bunyavanich, Supinda , Stokholm, Jakob , Esplugues, Ana , Milani, Lili A. , Jorgenson, Eric , Lominchar, Jesus V. T. , J

in 45/43 / 631/208/205/2138 / 692/699/4033 / Atopic / Atopic dermatitis / Basic Medicine / Black People / Deoxyribonuclease / Dermatitis / Dermatitis, Atopic - genetics / Dermatologi och venereologi / Dermatology and Venereal Diseases / Eczema / Gene loci / Genes / Genetic Predisposition to Disease / Genetic Predisposition to Disease - genetics / genetics / Genetics and Genomics / Genetik och genomik / Genome-wide association studies / Genome-Wide Association Study / Genomes / Hispanic or Latino / Hispanic or Latino - genetics / Humanities and Social Sciences / Humans / Hypersensitivity / Immunoregulation / Inflammation / Medical and Health Sciences / Medical Genetics and Genomics (including Gene Therapy) / Medicin och hälsovetenskap / Medicinsk genetik och genomik (Här ingår: Genterapi) / Medicinska och farmaceutiska grundvetenskaper / Meta-analysis / multidisciplinary / Polymorphism / Polymorphism, Single Nucleotide / Science / Science (multidisciplinary) / Single Nucleotide / Skin diseases

2023

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

2023

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2023

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Journal Article

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

Espuela-Ortiz, Antonio,

Kadalayil, Latha,

Paternoster, Lavinia,

Shringarpure, Suyash S.,

Sobczyk, Maria K.,

Choquet, Hélène,

Titcombe, Philip,

Terao, Chikashi,

Kårhus, Line L.,

Ahluwalia, Tarunveer S.,

Sleiman, Patrick M.,

Johansson, Stefan,

Hveem, Kristian,

Probst-Hensch, Nicole,

Ullemar, Vilhelmina,

Sly, Peter D.,

Mitchell, Ruth,

Almqvist, Catarina,

Hoffmann, Thomas,

Boomsma, Dorret I.,

Medina-Gomez, Carolina,

Esko, Tõnu,

Standl, Marie,

Nelis, Mari,

Bork-Jensen, Jette,

Vonk, Judith M.,

Magnusson, Patrik K. E.,

Duan, Jiasong,

Mägi, Reedik,

Grarup, Niels,

Arnau-Soler, Aleix,

Njølstad, Pål,

Hu, Chen,

Lau, Susanne,

Feenstra, Bjarke,

Brown, Sara J.,

Simpson, Angela,

Hakonarson, Hakon,

Linneberg, Allan,

Brumpton, Ben M.,

German, Chris,

Pino-Yanes, Maria,

Burchard, Esteban G.,

Kumar, Ashish,

Thomas, Laurent F.,

Wang, Carol A.,

Hadebe, Sabelo,

Flatley, Christopher,

Jeong, Ayoung,

Ballardini, Natalia,

Qi, Cancan,

Gong, Tong,

Murray, Clare,

Hottenga, Jouke J.,

Müller-Nurasyid, Martina,

Jarvis, Deborah,

Bunyavanich, Supinda,

Stokholm, Jakob,

Esplugues, Ana,

Milani, Lili A.,

Jorgenson, Eric,

Lominchar, Jesus V. T.,

2023

Overview

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. The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ Atopic