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

Mahmoud, Osama and Dudbridge, Frank and Davey Smith, George and Munafo, Marcus and Tilling, Kate (2022) 'A robust method for collider bias correction in conditional genome-wide association studies.' Nature Communications, 13 (1). 619-. ISSN 2041-1723

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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: Humans; Breast Neoplasms; Genetic Predisposition to Disease; Body Mass Index; Fasting; Risk Factors; Computational Biology; Phenotype; Polymorphism, Single Nucleotide; Algorithms; Genome-Wide Association Study; Machine Learning; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Bias
Divisions: Faculty of Science and Health
Faculty of Science and Health > Mathematical Sciences, Department of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 04 Feb 2022 11:11
Last Modified: 18 Aug 2022 12:26

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