Leveraging polygenic functional enrichment to improve GWAS power
Armin P. Schoech,
Posted 20 Nov 2017
bioRxiv DOI: 10.1101/222265 (published DOI: 10.1016/j.ajhg.2018.11.008)
Posted 20 Nov 2017
Functional genomics data has the potential to increase GWAS power by identifying SNPs that have a higher prior probability of association. Here, we introduce a method that leverages polygenic functional enrichment to incorporate coding, conserved, regulatory and LD-related genomic annotations into association analyses. We show via simulations with real genotypes that the method, Functionally Informed Novel Discovery Of Risk loci (FINDOR), correctly controls the false-positive rate at null loci and attains a 9-38% increase in the number of independent associations detected at causal loci, depending on trait polygenicity and sample size. We applied FINDOR to 27 independent complex traits and diseases from the interim UK Biobank release (average N=130K). Averaged across traits, we attained a 13% increase in genome-wide significant loci detected (including a 20% increase for disease traits) compared to unweighted raw p-values that do not use functional data. We replicated the novel loci in independent UK Biobank and non-UK Biobank data, yielding a highly statistically significant replication slope (0.66-0.69) in each case. Finally, we applied FINDOR to the full UK Biobank release (average N=416K), attaining smaller relative improvements (consistent with simulations) but larger absolute improvements, detecting an additional 583 GWAS loci. In conclusion, leveraging functional enrichment using our method robustly increases GWAS power.
- Downloaded 1,379 times
- Download rankings, all-time:
- Site-wide: 16,530
- In genetics: 747
- Year to date:
- Site-wide: 132,371
- Since beginning of last month:
- Site-wide: 94,773
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!