We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
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We thank all participants who provided data for each study and also thank our valued colleagues who contributed to data collection and phenotypic characterization of clinical samples, genotyping, and analysis of individual datasets. Detailed acknowledgments and funding for individual studies can be found in the Supplementary Note.
The authors affiliated with deCODE (D.F.G., I.J., K.S., U.T., and G.T.) are employees of deCODE genetics/Amgen. All other coauthors have no conflicts of interest to declare.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Figures 1–7, Supplementary Tables 3, 5–7, 9, 10, 12–17, 20 and 21, and Supplementary Note.
Description of TAGC studies included in the meta-analysis.
Information on genotyping methods, imputation, and statistical analysis by study. Details and references for each study are in the Supplementary Note.
Genome-wide significant SNPs (Prandom ≤ 5 × 10−8) in the European-ancestry meta-analysis.
Genome-wide significant SNPs (Prandom ≤ 5 × 10−8) in the multi-ancestry meta-analysis.
Association of 17q12-21 SNPs with asthma in multi-ancestry and pediatric meta-analyses.
Overlap between TAGC asthma-association signals (Prandom <10−3) and GWAS signals with diseases/traits in the GWAS catalog.
Enrichment of asthma risk loci in promoter and enhancer marks by cell type. The results presented in this table are for 16 out of the 18 asthma loci shown in Table 1. The 6p21.33 and 6p21.32 loci spanning the HLA complex were excluded because of high variability and LD in the region. Enhancer and promoter marks were defined using the ChromHMM 15-state model applied to 127 ROADMAP/ENCODE reference epigenomes (PMID 25693563).
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Demenais, F., Margaritte-Jeannin, P., Barnes, K.C. et al. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nat Genet 50, 42–53 (2018). https://doi.org/10.1038/s41588-017-0014-7
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