Grosche, Sarah and Marenholz, Ingo and Esparza-Gordillo, Jorge and Arnau-Soler, Aleix and Pairo-Castineira, Erola and Rueschendorf, Franz and Ahluwalia, Tarunveer S. and Almqvist, Catarina and Arnold, Andreas and Baurecht, Hansjoerg and Bisgaard, Hans and Bonnelykke, Klaus and Brown, Sara J. and Bustamante, Mariona and Curtin, John A. and Custovic, Adnan and Dharmage, Shyamali C. and Esplugues, Ana and Falchi, Mario and Fernandez-Orth, Dietmar and Ferreira, Manuel A. R. and Franke, Andre and Gerdes, Sascha and Gieger, Christian and Hakonarson, Hakon and Holt, Patrick G. and Homuth, Georg and Hubner, Norbert and Hysi, Pirro G. and Jarvelin, Marjo-Riitta and Karlsson, Robert and Koppelman, Gerard H. and Lau, Susanne and Lutz, Manuel and Magnusson, Patrik K. E. and Marks, Guy B. and Mueller-Nurasyid, Martina and Noethen, Markus M. and Paternoster, Lavinia and Pennell, Craig E. and Peters, Annette and Rawlik, Konrad and Robertson, Colin F. and Rodriguez, Elke and Sebert, Sylvain and Simpson, Angela and Sleiman, Patrick M. A. and Standl, Marie and Stoelzl, Dora and Strauch, Konstantin and Szwajda, Agnieszka and Tenesa, Albert and Thompson, Philip J. and Ullemar, Vilhelmina and Visconti, Alessia and Vonk, Judith M. and Wang, Carol A. and Weidinger, Stephan and Wielscher, Matthias and Worth, Catherine L. and Xu, Chen-Jian and Lee, Young-Ae (2021) Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4. NATURE COMMUNICATIONS, 12 (1): 6618. ISSN 2041-1723
Full text not available from this repository. (Request a copy)Abstract
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. Genetic studies of eczema to date have mostly explored common genetic variation. Here, the authors perform a large meta-analysis for common and rare variants and discover 8 loci associated with eczema. Over 20% of the heritability of the condition is attributable to rare variants.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; ATOPIC-DERMATITIS; SUSCEPTIBILITY LOCI; RISK LOCI; DISEASE; METAANALYSIS; SEQUENCE; ASTHMA; KERATINOCYTES; PHOSPHATASE |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2022 05:27 |
| Last Modified: | 05 Jul 2022 05:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48222 |
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