Year: 2024
Type: preprint
Abstract: Omics-based association studies typically consider the marginal effects of a feature, such as CpG DNA methylation, on a trait (e.g, independent models for each feature). Although some methods can assess all features together in joint and conditional estimation, this is currently done on a trait-by-trait basis. Here, we introduce MAJA, a method to learn shared and outcome-specific effects for multiple traits in multi-omics data. MAJA determines the unique contribution of individual loci, genes, or molecular pathways, to variation in one or more traits, conditional on all other measured “omics” data genome-wide. Simulations show MAJA accurately finds shared and distinct associations between omics-data and multiple traits and estimates omics-specific (co)variances, allowing for sparsity and correlations within the data. Applying MAJA to 12 outcome traits in Generation Scotland methylation data (n=18,264), we find novel shared epigenetic pathways among cholesterol metabolism, osteoarthritis, blood pressure and asthma. In contrast to marginal testing, we find only 10 CpG probes with significant effects above the genome-wide background. This highlights the need for joint association testing in highly correlated methylation data from whole blood and for studies of increased sample size in order to refine epigenomic associations in observational data.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, Scottish Government, Royal College of Physicians of Edinburgh, Institute of Science and Technology Austria, Scottish Funding Council, Age UK, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, University of Queensland, Centre for Cognitive Ageing and Cognitive Epidemiology, Directorate for Biological Sciences, Chief Scientist Office, Scottish Government Health and Social Care Directorate, Medical Research Council, Economic and Social Research Council
Awards: G1255019943, Nichtlineare Optik und zeitaufgelöste Spektroskopie von Molekülenund Festkörpern., Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III, G2064318019, G2277832307, G2437620908, Factors of biological ageing: does it all go together when it goes?, G259633682, G3906703801, G3996179666, Stratifying Resilience and Depression Longitudinally (STRADL), Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: IV, Improving estimation and prediction of common complex disease risk, Translational Neuroscience 2 (TN2), G5931154709, G6671908157, G718988473, G7749460998, G839044655, G8724570043, Translational Neuroscience 2 (TN2), Beyond Reality? Virtuality and Experience
OpenAlex ID: W4394840272