A robust method for collider bias correction in conditional genome-wide association studies

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Mahmoud, O. ORCID: https://orcid.org/0000-0003-0342-6704, Dudbridge, F., Davey Smith, G., Munafo, M. and Tilling, K. (2022) A robust method for collider bias correction in conditional genome-wide association studies. Nature Communications, 13 (1). ISSN 2041-1723

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Abstract

Estimated genetic associations with prognosis, or conditional on a phenotype (e.g. disease incidence), may be affected by collider bias, whereby conditioning on the phenotype induces associations between causes of the phenotype and prognosis. We propose a method, ‘Slope-Hunter’, that uses model-based clustering to identify and utilise the class of variants only affecting the phenotype to estimate the adjustment factor, assuming this class explains more variation in the phenotype than any other variant classes. Simulation studies show that our approach eliminates the bias and outperforms alternatives even in the presence of genetic correlation. In a study of fasting blood insulin levels (FI) conditional on body mass index, we eliminate paradoxical associations of the underweight loci: COBLLI; PPARG with increased FI, and reveal an association for the locus rs1421085 (FTO). In an analysis of a case-only study for breast cancer mortality, a single region remains associated with more pronounced results.

Item Type: Article
Uncontrolled Keywords: das in place,oncoarray-and-combined-summary-result”. source data are provided with this paper. ,/dt/atira/pure/keyword/DAStatement/das_in_place
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 26 Oct 2026 09:48
Last Modified: 26 Oct 2026 10:08
URI: https://ueaeprints.uea.ac.uk/id/eprint/104837
DOI: 10.1038/s41467-022-28119-9

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