Simultaneous estimation of bi-directional causal effects and heritable confounding from GWAS summary statistics.

Details

Serval ID
serval:BIB_E3BA5FA37823
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Simultaneous estimation of bi-directional causal effects and heritable confounding from GWAS summary statistics.
Journal
Nature communications
Author(s)
Darrous L., Mounier N., Kutalik Z.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
14/12/2021
Peer-reviewed
Oui
Volume
12
Number
1
Pages
7274
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Mendelian Randomisation (MR) is an increasingly popular approach that estimates the causal effect of risk factors on complex human traits. While it has seen several extensions that relax its basic assumptions, most suffer from two major limitations; their under-exploitation of genome-wide markers, and sensitivity to the presence of a heritable confounder of the exposure-outcome relationship. To overcome these limitations, we propose a Latent Heritable Confounder MR (LHC-MR) method applicable to association summary statistics, which estimates bi-directional causal effects, direct heritabilities, and confounder effects while accounting for sample overlap. We demonstrate that LHC-MR outperforms several existing MR methods in a wide range of simulation settings and apply it to summary statistics of 13 complex traits. Besides several concordant results with other MR methods, LHC-MR unravels new mechanisms (how disease diagnosis might lead to improved lifestyle) and reveals new causal effects (e.g. HDL cholesterol being protective against high systolic blood pressure), hidden from standard MR methods due to a heritable confounder of opposite effect direction.
Pubmed
Open Access
Yes
Create date
20/12/2021 13:42
Last modification date
24/12/2021 7:34
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