Multi-ethnic genome-wide association study for atrial fibrillation



Roselli, Carolina, Chaffin, Mark D, Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M, Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D, Aragam, Krishna G
et al (show 208 more authors) (2018) Multi-ethnic genome-wide association study for atrial fibrillation. Nature Genetics, 50. 1225 - 1233.

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Broad_AF_main_text_03_08_2018.pdf - Accepted Version

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Broad_AF_supplement_03_08_2018.pdf - Accepted Version

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Broad_AF_integrated_supplementary_figures_03_08_2018.doc - Accepted Version

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Figure 1. Study and analysis flowchart.ps - Accepted Version

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Figure 2. Manhattan plot of combined-ancestry meta-analysis.ai - Accepted Version

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Figure 3. Volcano plot of transcriptome-wide analysis from human heart tissues.ps - Accepted Version

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Figure 4. Cross-trait associations of AF risk variants with AF risk factors in the UK Biobank.ai - Accepted Version

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Supplementary Table 3. Known loci in combined ancestry meta-analysis.xlsx - Accepted Version

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Supplementary Table 4. Gene set enrichment analysis results for combined ancestry meta-analysis.xlsx - Accepted Version

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Supplementary Table 5. Novel and known loci in ancestry specific meta-analyses.xlsx - Accepted Version

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Supplementary Table 7. Loci with multiple signals identified by conditional and joint analysis for European ancestry meta-analysis.xlsx - Accepted Version

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Supplementary Table 9. Chromatin states for sentinel variants and proxies from Roadmap Epigenomics across all tissues and heart.xlsx - Accepted Version

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Supplementary Table 11. Significant cis-eQTLs for sentinel variants from combined ancestry meta-analysis in GTEx heart tissues.xlsx - Accepted Version

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Supplementary Table 11. Significant cis-eQTLs for sentinel variants from combined ancestry meta-analysis in GTEx heart tissues.xlsx - Accepted Version

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Supplementary Table 12. Probable AF susceptibility genes for loci from combined ancestry meta-analysis.xlsx - Accepted Version

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Supplementary Table 13. Transcriptome-wide results based on summary level data from combined ancestry meta-analysis.xlsx - Accepted Version

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Supplementary Table 14. Association to diseases and traits in NHGRI-EBI GWAS catalog for sentinel variants or proxies from combined ancestry meta-analysis.xlsx - Accepted Version

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Supplementary Table 15. PheWAS results in UK Biobank for sentinel variants from combined ancestry meta-analysis.xlsx - Accepted Version

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Supplementary Table 16. 134 loci associated with atrial fibrillation.xlsx - Accepted Version

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Supplementary Table 17. Baseline summary for GWAS.xlsx - Accepted Version

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Supplementary Table 18. GWAS summary on genotyping, QC, imputation and analysis per study.xlsx - Accepted Version

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Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Item Type: Article
Uncontrolled Keywords: Diseases, Genetics
Depositing User: Symplectic Admin
Date Deposited: 13 Aug 2018 08:33
Last Modified: 22 Oct 2020 01:10
DOI: 10.1038/s41588-018-0133-9
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3024835