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Grosche, S.* ; Marenholz, I.* ; Esparza-Gordillo, J.* ; Arnau-Soler, A.* ; Pairo-Castineira, E.* ; Rüschendorf, F.* ; Ahluwalia, T.S.* ; Almqvist, C.* ; Arnold, A.* ; Baurecht, H.* ; Bisgaard, H.* ; Bønnelykke, K.* ; Brown, S.J.* ; Bustamante, M.* ; Curtin, J.A.* ; Custovic, A.* ; Dharmage, S.C.* ; Esplugues, A.* ; Falchi, M.* ; Fernandez-Orth, D.* ; Ferreira, M.A.R.* ; Franke, A.* ; Gerdes, S.* ; Gieger, C. ; Hakonarson, H.* ; Holt, P.G.* ; Homuth, G.* ; Hubner, N.* ; Hysi, P.G.* ; Jarvelin, M.R.* ; Karlsson, R.* ; Koppelman, G.H.* ; Lau, S.* ; Lutz, M. ; Magnusson, P.K.E.* ; Marks, G.B.* ; Müller-Nurasyid, M. ; Nöthen, M.M.* ; Paternoster, L.* ; Pennell, C.E.* ; Peters, A. ; Rawlik, K.* ; Robertson, C.F.* ; Rodriguez, E.* ; Sebert, S.* ; Simpson, A.* ; Sleiman, P.M.A.* ; Standl, M. ; Stölzl, D.* ; Strauch, K. ; Szwajda, A.* ; Tenesa, A.* ; Thompson, P.J.* ; Ullemar, V.* ; Visconti, A.* ; Vonk, J.M.* ; Wang, C.A.* ; Weidinger, S.* ; Wielscher, M.* ; Worth, C.L.* ; Xu, C.J.* ; Lee, Y.A.*

Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4.

Nat. Commun. 12:6618 (2021)
Publ. Version/Full Text DOI
Open Access Gold
Creative Commons Lizenzvertrag
Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Atopic-dermatitis; Susceptibility Loci; Risk Loci; Disease; Metaanalysis; Sequence; Asthma; Keratinocytes; Phosphatase
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 6618 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Grants Projekt DEAL