B2860 - DNA methylation from birth to adolescence in Generation R and ALSPAC - 26/04/2017

B number: 
B2860
Principal applicant name: 
Matthew Suderman | Integrative Epidemiology Unit (United Kingdom)
Co-applicants: 
Professor Caroline Relton, Professor Kate Tilling, Dr Lotte Houtepen, Dr Esther Walton, Dr James Staley, Professor Henning Tiemeier, Mr Alexander Neumann, Ms Rosa H. Mulder, Dr Jolien Rijlaarsdam, Dr Charlotte Cecil
Title of project: 
DNA methylation from birth to adolescence in Generation R and ALSPAC
Proposal summary: 

DNA methylation is a stable but reversible chemical modification of DNA that changes the way DNA sequence is interpreted within a cell. It plays multiple key roles in human biology, acting for example as a mechanism for allowing cells to differentiate into specific types (e.g. skin cells) and to maintain their differentiated identities. It was recently discovered that DNA methylation patterns in the genome change with age and can be used to accurately estimate the age of a person. Although many studies have investigated these estimates in great detail, particularly the cases where there is a discrepancy between actual and estimated age, few studies have more broadly considered the ways that DNA methylation changes throughout the lifecourse and how those changes relate to development and aging. The few that have either consider only aging in adulthood or short periods such as puberty in childhood. We propose to comprehensively investigate DNA methylation change from birth to adolescence using DNA methylation profiles from ALSPAC measured at birth, age 7y and age 15-17y (as part of ARIES: Accessible Resource for Integrated Epigenomic Studies) and from the Generation R cohort study in Rotterdam (http://www.generationr.nl/) measured at birth, age 6y and age 9y. We will use statistical models to identify regions of the genome with similar patterns of change over time (e.g. consistently increasing or decreasing) both within and between the sexes and then investigate the possible biological implications of these patterns by linking them to known developmental stages and the functions of affected genes. This set of regions and their patterns will inform future follow-up studies investigating molecular associations with childhood exposures, phenotypes and outcomes.

Date proposal received: 
Wednesday, 8 March, 2017
Date proposal approved: 
Wednesday, 8 March, 2017
Keywords: 
Genetics, Epigenetics, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Genetics - e.g. epigenetics, mendelian randomisation, UK10K, sequencing, etc., Puberty, Sex differences