Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults
Year: 2020
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets. METHODS: In this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). RESULTS: We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn's disease. CONCLUSIONS: Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.
Source: Genome Medicine
Authors: Robert F. Hillary, Daniel Trejo-Banos, Athanasios Kousathanas, Daniel L. McCartney, Sarah E. Harris, Anna J. Stevenson, Marion Patxot, Sven Erik Ojavee, Qian Zhang, David C. Liewald, Craig W. Ritchie, Kathryn L. Evans, Elliot M. Tucker-Drob, Naomi R. Wray, Allan F. McRae, Peter M. Visscher, Ian J. Deary, Matthew R. Robinson, Riccardo E. Marioni
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,290
Funders: Wellcome Trust, Age UK, University of Edinburgh, University of Queensland, Alzheimer’s Research UK, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, Australian Research Council, National Health and Medical Research Council, National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Centre for Cognitive Ageing & Cognitive Epidemiology, Genetics of DNA Methylation and Its Role in Disease Susecptibility, Translational Neuroscience - training the next generation of basic neuroscientists to embrace clinical research., G2165108532, Causes and consequence of human trait variation, G2730595978, G2954243588, Phenotypic profiling from DNA using genetic and epigenetic information, G3229869697, Inheritance of DNA methylation, G3561803360, G3649208995, G3669141092, University of Edinburgh - Translational Neuroscience, G3868569194, Complex trait genomics, Using genomics to understand psychiatric disorders, G3996179666, Stratifying Resilience and Depression Longitudinally (STRADL), University of Edinburgh - Translational Neuroscience, G4519464314, G4527525017, G4641403149, G483280169, G4942547004, G5026251150, G5067462658, G5139826593, G5490630913, G5834621717, G6223125567, Neurogenetics and Statistical Genomics, G666546157, G6868616705, A genome-wide association study of non-pathological cognitive ageing, G718988473, Evaluating Longitudinal Changes in the Human Structural Connectome in Relation to Cognitive Aging, G7653015201, G829891318, CAGE: Consortium for the Architecture of Gene Expression, G9000063527, G9000159272
OpenAlex ID: W3041831590