The flashfm approach for fine-mapping multiple quantitative traits


Change log
Authors
Newcombe, P. 
Sandhu, M. 
Abstract

Abstract: Joint fine-mapping that leverages information between quantitative traits could improve accuracy and resolution over single-trait fine-mapping. Using summary statistics, flashfm (flexible and shared information fine-mapping) fine-maps signals for multiple traits, allowing for missing trait measurements and use of related individuals. In a Bayesian framework, prior model probabilities are formulated to favour model combinations that share causal variants to capitalise on information between traits. Simulation studies demonstrate that both approaches produce broadly equivalent results when traits have no shared causal variants. When traits share at least one causal variant, flashfm reduces the number of potential causal variants by 30% compared with single-trait fine-mapping. In a Ugandan cohort with 33 cardiometabolic traits, flashfm gave a 20% reduction in the total number of potential causal variants from single-trait fine-mapping. Here we show flashfm is computationally efficient and can easily be deployed across publicly available summary statistics for signals in up to six traits.

Description

Funder: “Expanding excellence in England” award from Research England

Keywords
Article, /631/208/205/2138, /631/208/480, /45/43, /141, /139, article
Journal Title
Nature Communications
Conference Name
Journal ISSN
2041-1723
Volume Title
12
Publisher
Nature Publishing Group UK
Sponsorship
RCUK | Medical Research Council (MRC) (MC UU 00002/9, MC_UU_00002/4, MR/R021368/1)
DH | National Institute for Health Research (NIHR) (BRC-1215-20014, BRC-1215-20014, BRC-1215-20014)
Wellcome Trust (Wellcome) (WT107881)