ANNIVERSARY LECTURE 5: Atopic eczema: how genetics helps us to understand this very complex trait
Sara J Brown is Professor of Molecular and Genetic Dermatology in the University of Dundee, Scotland and a Wellcome Trust Senior Research Fellow. During her clinical training in Newcastle, England, Sara became interested in paediatric dermatology and genetic mechanisms in skin, at the time of the ground-breaking discovery of FLG mutations (by Irwin McLean and colleagues). Sara conducted the first population-based cohort study to show that FLG null mutations affect risk of the milder eczema phenotype that is very prevalent in the community, in addition to severe disease.
Sara continued her research in atopic eczema and she has developed a pipeline of discovery from genomic and genetic variation at the population level, to subgroups in vivo and mechanistic studies in vitro. The ultimate aim is to understand genetic risk mechanisms as new therapeutic targets. Throughout this work Sara has been inspired by patients and families who live with the challenges of atopic disease.
Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, Wilson IJ, Burn J, Reynolds NJ, McLean WHI and Cordell HJ. Filaggrin null mutations and childhood atopic eczema: a population-based case-control study. J Allergy Clin Immunol 2008; 121(4):940-946.
Brown SJ, Kroboth K, Sandilands A, Campbell L, Pohler E, Kezic S, Cordell HJ, McLean WHI and Irvine AD. Intragenic copy number variation within filaggrin contributes to risk of atopic dermatitis with a dose-dependent effect. J Invest Dermatol 2012; 132(1):98-104.
Ellinghaus D et al., Fahy CM, Kabesch M, Brown S, McLean WH, Irvine AD, Schreiber S, Lee YA, Franke A, Weidinger S. High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet. 2013; 45(7):808-12.
Cole C, Kroboth K, Schurch NJ, Sandilands A, Sherstnev A, et al., Watson RM, McLean WHI, Barton GJ, Irvine AD, Brown SJ. Filaggrin-stratified transcriptome analysis of paediatric skin identifies mechanistic pathways in atopic dermatitis. J Allergy Clin Immunol. 2014; 134(1):82-91.
Baurecht H,* Hotze M,* Brand S, Büning C, Cormican P, Corvin A, Ellinghaus D, Ellinghaus E, Esparza-Gordillo J, Fölster-Holst R, Franke A, Gieger C, Hubner N, Illig T, Irvine AD, Kabesch M, Lee Y AE, Lieb W, Marenholz I, McLean WHI, Morris DW, Mrowietz U, Nair R, Nöthen MM, Novak N, O’Regan GM, PAGE consortium, Schreiber S, Smith C, Strauch K, Stuart PE, Trembath R, Tsoi LC, Weichenthal M, Barker J, Elder JT, Weidinger S,* Cordell HJ,* and Brown SJ.* [* contributed equally]. Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. Am J Hum Genet. 2015; 96(1):104-20. PMID:25574825
Paternoster L, Standl M, Waage J, Baurecht H et al. [148 other co-authors], Brown SJ, Heinrich J, Evans DM* and Weidinger S.* (joint senior authors*). Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015 Dec;47(12):1449-56. PMID: 26482879.
Lavinia Paternoster, Olga E.M. Savenije, Jon Heron, David M. Evans, Judith M. Vonk, Bert Brunekreef, Alet H. Wijga, A. John Henderson, Gerard H. Koppelman* and Sara J. Brown*. Identification of atopic dermatitis subgroups in children from two longitudinal birth cohorts. J Allergy Clin Immunol 2018;141(3):964-971.
Elias MS, Wright SC, Remenyi J, Abbott JC, Bray SE, Cole C, Edwards S, Gierlinski M, Glok M, McGrath JA, Nicholson WV, Paternoster L, Prescott AR, Have ST, Whitfield PD1, Lamond AI and Brown SJ. EMSY expression affects multiple components of skin barrier with relevance to atopic dermatitis. J Allergy Clin Immunol 2019;144(2):470-481.