B3961 - Integrating genetics epigenetics and metabolomics to identify early life origins of adult disease - 05/02/2022

B number: 
Principal applicant name: 
Joel Hirschhorn | Boston Children's Hospital/Broad Institute of MIT and Harvard (United States)
Dr. Mary Elizabeth Patti, Dr. Anders Eliasen
Title of project: 
Integrating genetics, epigenetics and metabolomics to identify early life origins of adult disease
Proposal summary: 

We will use multiple types of data from children in ALSPAC and other childhood cohorts to ask what factors, already evident in children, are causal precursors of future disease. We will focus on molecules that circulate in the blood (metabolites), factors inherited in the genome (genetic variants), and special modifications of the genome (epigenetics, methylation). By combining data from children for genetic variants, epigenetics and metabolites, we can ask whether there are particular metabolites or epigenetic factors that are causal precursors of diseases like obesity, coronary artery disease (CAD), and type 2 diabetes (T2D). Understanding the early causal factors of future disease could guide earlier and therefore potentially more effective interventions.

Impact of research: 
We hope to identify metabolic and/or epigenetic childhood markers that are associated with genetic risk of future cardiometabolic disease and to assess them for evidence of causality using Mendelian randomization. If successful, these biomarkers may be part of early screening to guide intervention, and if causal may give rise to new therapeutic hypotheses that are based in causal mechanisms.
Date proposal received: 
Tuesday, 21 December, 2021
Date proposal approved: 
Tuesday, 21 December, 2021
Genetics, Diabetes, Obesity, coronary artery disease hyperlipidemia central adiposity nonalcoholic fatty liver disease metabolic syndrome hypertension, GWAS, Metabolomics, Statistical methods, Methylation (epigenetics), Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Mendelian randomisation, Metabolic - metabolism, Nutrition - breast feeding, diet, Statistical methods, Blood pressure, BMI, Cardiovascular, Epigenetics, Genetic epidemiology, Genetics, Genomics, Genome wide association study