Evaluating the performance of fine-mapping strategies at common variant GWAS Loci

van de Bunt, Martijn, Cortes, Adrian, Brown, Matthew A., Morris, Andrew P., McCarthy, Mark I., IGAS Consortium, Hadler, Johanna, Robinson, Philip C., Leo, Paul, Cremin, Katie, Pryce, Karena, Harris, Jessica, Bradbury, Linda A., Kenna, Tony J. and Yang, Jian (2015) Evaluating the performance of fine-mapping strategies at common variant GWAS Loci. PL o S Genetics, 11 9: 1-14. doi:10.1371/journal.pgen.1005535

Author van de Bunt, Martijn
Cortes, Adrian
Brown, Matthew A.
Morris, Andrew P.
McCarthy, Mark I.
IGAS Consortium
Hadler, Johanna
Robinson, Philip C.
Leo, Paul
Cremin, Katie
Pryce, Karena
Harris, Jessica
Bradbury, Linda A.
Kenna, Tony J.
Yang, Jian
Title Evaluating the performance of fine-mapping strategies at common variant GWAS Loci
Journal name PL o S Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2015-09-01
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1005535
Open Access Status DOI
Volume 11
Issue 9
Start page 1
End page 14
Total pages 14
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 1105 Ecology, Evolution, Behavior and Systematics
1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
1306 Cancer Research
Abstract The growing availability of high-quality genomic annotation has increased the potential for mechanistic insights when the specific variants driving common genome-wide association signals are accurately localized. A range of fine-mapping strategies have been advocated, and specific successes reported, but the overall performance of such approaches, in the face of the extensive linkage disequilibrium that characterizes the human genome, is not well understood. Using simulations based on sequence data from the 1000 Genomes Project, we quantify the extent to which fine-mapping, here conducted using an approximate Bayesian approach, can be expected to lead to useful improvements in causal variant localization. We show that resolution is highly variable between loci, and that performance is severely degraded as the statistical power to detect association is reduced. We confirm that, where causal variants are shared between ancestry groups, further improvements in performance can be obtained in a trans-ethnic fine-mapping design. Finally, using empirical data from a recently published genome-wide association study for ankylosing spondylitis, we provide empirical confirmation of the behaviour of the approximate Bayesian approach and demonstrate that seven of twenty-six loci can be fine-mapped to fewer than ten variants.
Keyword Inflammatory bowel disease
Genetic architecture
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 25 Oct 2015, 10:21:51 EST by System User on behalf of Scholarly Communication and Digitisation Service