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

被引：58

作者：

Budu-Aggrey, Ashley ^{[1
,2
]}

Kilanowski, Anna ^{[3
,4
,5
]}

Sobczyk, Maria K. ^{[1
,2
]}

Shringarpure, Suyash S. ^{[6
]}

Mitchell, Ruth ^{[1
,2
]}

Reis, Kadri ^{[7
]}

Reigo, Anu ^{[7
]}

Maegi, Reedik ^{[7
]}

Nelis, Mari ^{[7
,8
]}

Tanaka, Nao ^{[9
,10
]}

Brumpton, Ben M. ^{[11
,12
,13
]}

Thomas, Laurent F. ^{[11
,14
,15
,16
]}

Sole-Navais, Pol ^{[17
]}

Flatley, Christopher ^{[17
]}

Espuela-Ortiz, Antonio ^{[18
]}

Herrera-Luis, Esther ^{[18
]}

Lominchar, Jesus V. T. ^{[19
]}

Bork-Jensen, Jette ^{[19
]}

Marenholz, Ingo ^{[20
,21
]}

Arnau-Soler, Aleix ^{[20
,21
]}

Jeong, Ayoung ^{[22
,23
]}

Fawcett, Katherine A. ^{[24
]}

Baurecht, Hansjorg ^{[25
]}

Rodriguez, Elke ^{[26
]}

Alves, Alexessander Couto ^{[27
]}

Kumar, Ashish ^{[28
]}

Sleiman, Patrick M. ^{[29
,30
,31
]}

Chang, Xiao ^{[29
]}

Medina-Gomez, Carolina ^{[32
,33
]}

Hu, Chen ^{[32
,34
]}

Xu, Cheng-jian ^{[35
,36
,37
,38
]}

Qi, Cancan ^{[35
,36
]}

El-Heis, Sarah ^{[39
]}

Titcombe, Philip ^{[39
]}

Antoun, Elie ^{[40
,41
]}

Fadista, Joao ^{[42
,43
,44
,45
]}

Wang, Carol A. ^{[46
,47
]}

Thiering, Elisabeth ^{[3
,4
]}

Wu, Baojun ^{[48
]}

Kress, Sara ^{[49
]}

Kothalawala, Dilini M. ^{[50
,51
]}

Kadalayil, Latha ^{[50
]}

Duan, Jiasong ^{[52
]}

Zhang, Hongmei ^{[52
]}

Hadebe, Sabelo ^{[53
]}

Hoffmann, Thomas ^{[54
,55
]}

Jorgenson, Eric ^{[56
]}

Choquet, Helene ^{[57
]}

Risch, Neil ^{[54
,55
]}

Njolstad, Pal ^{[58
,59
]}

机构：

[1] Univ Bristol, Bristol Med Sch, Med Res Council Integrat Epidemiol Unit, Bristol, Avon, England

[2] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[3] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[4] Univ Munich, Med Ctr, Dr von Hauner Childrens Hosp, Div Metab & Nutr Med, Munich, Germany

[5] Ludwig Maximilians Univ Munchen, Pettenkofer Sch Publ Hlth, Munich, Germany

[6] 23andMe Inc, Sunnyvale, CA USA

[7] Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia

[8] Univ Tartu, Core Facil Genom, Tartu, Estonia

[9] RIKEN, Ctr Integrat Med Sci, Lab Stat & Translat Genet, Yokohama, Kanagawa, Japan

[10] Tokyo Med & Dent Univ TMDU, Grad Sch Med & Dent Sci, Dept Rheumatol, Tokyo, Japan

[11] Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth & Nursing, KG Jebsen Ctr Genet Epidemiol, N-7030 Trondheim, Norway

[12] Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth & Nursing, HUNT Res Ctr, N-7600 Levanger, Norway

[13] Trondheim Reg & Univ Hosp, St Olavs Hosp, Clin Med, N-7030 Trondheim, Norway

[14] NTNU Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway

[15] Norwegian Univ Sci & Technol, NTNU, BioCore Bioinformat Core Facil, Trondheim, Norway

[16] Trondheim Reg & Univ Hosp, St Olavs Hosp, Clin Lab Med, Trondheim, Norway

[17] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden

[18] Univ La Laguna, Dept Biochem Microbiol Cell Biol & Genet, Genom & Hlth Grp, Tenerife, Spain

[19] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark

[20] Max Delbruck Ctr Mol Med, Berlin, Germany

[21] Charite Univ Med Berlin, Expt & Clin Res Ctr, Clin Pediat Allergy, Berlin, Germany

[22] Swiss Trop & Publ Hlth Inst, CH-4123 Basel, Switzerland

[23] Univ Basel, CH-4001 Basel, Switzerland

[24] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England

[25] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany

[26] Univ Hosp Schleswig Holstein, Dept Dermatol & Allergy, Kiel, Germany

[27] Univ Surrey, Sch Biosci & Med, Guildford, Surrey, England

[28] Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Solna, Sweden

[29] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[30] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[31] Rhythm Pharmaceut, 222 Berkley St, Boston, MA 02116 USA

[32] Univ Med Ctr Rotterdam, Generat R Study Grp, Erasmus MC, Rotterdam, Netherlands

[33] Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands

[34] Univ Med Ctr Rotterdam, Dept Dermatol, Erasmus MC, Rotterdam, Netherlands

[35] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergy, Groningen, Netherlands

[36] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands

[37] Ctr Individualized Infect Med, Hannover, Germany

[38] TWINCORE, Ctr Expt & Clin Infect Res, Hannover, Germany

[39] Univ Southampton, MRC Lifecourse Epidemiol Ctr, Southampton, Hants, England

[40] Univ Southampton, Fac Med, Southampton, Hants, England

[41] Univ Southampton, Inst Dev Sci, Southampton, Hants, England

[42] Dept Bioinformat & Data Min, Malov, Denmark

[43] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark

[44] Lund Univ, Ctr Diabet, Dept Clin Sci, Malmo, Sweden

[45] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[46] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia

[47] Hunter Med Res Inst, Newcastle, NSW, Australia

[48] Henry Ford Hlth, Dept Med, Ctr Individualized & Genom Med Res CIGMA, Detroit, MI 48104 USA

[49] IUF Leibniz Res Inst Environm Med, Environm Epidemiol Lung Brain & Skin Aging, Dusseldorf, Germany

[50] Univ Southampton, Human Dev & Hlth, Fac Med, Southampton, Hants, England

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

英国惠康基金; 芬兰科学院; 英国医学研究理事会; 欧洲研究理事会; 欧盟地平线“2020”;

关键词：

SUSCEPTIBILITY LOCI; GENE-EXPRESSION; GWAS; FILAGGRIN; TRANSCRIPTOME; REGRESSION; CHILDREN; VARIANTS; PATHWAYS; REVEALS;

D O I：

10.1038/s41467-023-41180-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：18

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