European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.
Ashley Budu-AggreyAnna KilanowskiMaria K Sobczyknull nullSuyash S ShringarpureRuth E MitchellKadri ReisAnu Reigonull nullReedik MägiMari NelisNao TanakaBen Michael BrumptonLaurent F ThomasPol Sole NavaisChristopher FlatleyAntonio Espuela-OrtizEsther Herrera-LuisJesus V T LomincharJette Bork-JensenIngo MarenholzAleix Arnau-SolerAyoung JeongKatherine A FawcettHansjorg BaurechtElke RodriguezAlexessander Couto AlvesAshish KumarPatrick M SleimanXiao ChangCarolina Medina-GomezChen HuCheng-Jian XuCancan QiSarah El-HeisPhilip TitcombeElie AntounJoão FadistaCarol A WangElisabeth ThieringBaojun WuSara KressDilini M KothalawalaLatha KadalayilJiasong DuanHongmei ZhangSabelo HadebeThomas J HoffmannEric JorgensonHelene ChoquetNeil RischPal Rasmus NjolstadOle Andreas AndreassenStefan E JohanssonCatarina AlmqvistTong GongVilhelmina UllemarRobert KarlssonPatrik K E MagnussonAgnieszka SzwajdaEsteban González BurchardJacob P ThyssenTorben HansenLine L KårhusThomas M DantoftAlexander C S N JeanrenaudAhla GhauriAndreas ArnoldGeorg HomuthSusanne LauMarkus Maria NöthenNorbert HübnerMedea ImbodenAlessia ViscontiMario FalchiVeronique BataillePirro G HysiNatalia BallardiniDorret I BoomsmaJouke- Jan HottengaMartina Müller-NurasyidTarunveer Singh AhluwaliaJessica Lasky-SuBo Lund ChawesAnn-Marie Malby SchoosAna EspluguesMariona BustamanteBenjamin RabySyed ArshadChris GermanTõnu EskoLili A MilaniAndres MetspaluChikashi C TeraoKatrina AbuabaraMari LøsetKristian HveemBo JacobsonMaria Pino-YanesDavid P StrachanNiels GrarupAllan LinnebergYoung-Ae LeeNicole Probst-HenschStephan WeidingerMarjo-Riitta JarvelinErik MelénHakon H HakonarsonAlan D IrvineDeborah JarvisTamar E C NijstenLiesbeth DuijtsJudith E VonkGerard H KoppelmannKeith M GodfreySheila J BartonBjarke FeenstraCraig E PennellPeter D SlyPatrick G HoltL Keoki WilliamsHans BisgaardKlaus BønnelykkeJohn CurtinAngela SimpsonClare S MurrayTamara SchikowskiSupinda BunyavanichScott T WeissJohn W HollowayJosine L MinSara J BrownMarie StandlLavinia PaternosterPublished in: Nature communications (2023)
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.