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MRC Precision Medicine DTP: The Genomics of Birth Parameters and Cardiometabolic Disease: Reviving the Walker Birth Cohort


Project Description

Background. The Walker Birth cohort consists of 48,000 births in Tayside between 1952-1966, representing 75% of all births during this period (1). ~34K Walker babies, plus ~16K mothers and ~10K fathers were subsequently identified and CHI’d enabling record linkage to all current e-health data. The Walker babies are now aged 51-65, with their parents (if still alive) ranging in age from 69 to 101 years old; thus these babies and their parents are now of an age where cardiovascular, metabolic disease and cancer are highly prevalent. Importantly ~25% of the current Tayside population have contributed to the Tayside Bioresource, made up of a number of genomics resources including GoDARTS, GoSHARE and the Scottish Family Health Study (SFHS) and Walker babies and parents were targeted for recruitment to SFHS in Tayside. As a result we can now link genetic information on ~2500 Walker babies and/or their parents. Most of GoDARTS and SFHS are now GWAS’d enabling us to link neonatal birth records to health outcomes over 65 years of follow up. Such studies are timely. Working with the Early Growth Genetics (EGG) consortium, we recently published data identifying novel genes linking size at birth with adverse cardiometabolic outcomes including hypertension and coronary artery disease (2). Yet none of the contributing cohorts in EGG capture the breadth of neonatal phenotyping, and depth of morbidity data and duration of follow up in the Walker cohort, and few have information on mothers and fathers. This is a largely untapped resource that due to the availability of GWAS and the age (and hence likely morbidities) of the Walker babies is now ripe for investigation.
Aims
1. To establish a clean linked dataset in the Dundee HIC safe haven, linking the Walker cohort to SMR01, SMR06 (cancer registry), GRO (deaths) and other local Tayside datasets (including vascular lab data, ECHO data, ECG data, prescription encashment data) and genetic data (GoDARTS/SFHS/GoSHARE).
2. To investigate the association of placental weight and birth weight with cardiovascular and metabolic outcomes (Hypertension, Vascular disease, Cardiovascular Disease (CVD), Diabetes, Cancer)
3. To investigate the association of Genetic risk scores for type 2 diabetes, insulin resistance, hypertension, CVD, lipids and other traits on birth weight and placental weight; and the impact of birthweight Genetic risk scores on health outcomes. In this way causal relationships can be explored, and where possible formal Mendelian Randomisation will be undertaken.
Training outcomes
The student will learn many ‘big data’ skills. Working in the safe haven they will need to use SQL to link and manage the many large databases and undertake statistical analysis using R, STATA or SAS. They will learn skills in statistical genetics and causal inference analysis, and statistical methods in analyzing longitudinal data sets. In addition the epidemiological and genetic studies will likely point to novel biological mechanisms/processes within the cardio-metabolic disease and reproductive health space; this will fit well with the student’s research environment, embedded within the Centre for Cardiovascular Science, QMRI.
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This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location:

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you should contact the primary supervisor prior to making your application. Additional information on the application process if available from the link above.

For more information about Precision Medicine visit:

http://www.ed.ac.uk/usher/precision-medicine

Funding Notes

Start: September 2019

Qualifications criteria: Applicants applying for a MRC DTP in Precision Medicine studentship must have obtained, or will soon obtain, a first or upper-second class UK honours degree or equivalent non-UK qualifications, in an appropriate science/technology area.

Residence criteria: The MRC DTP in Precision Medicine grant provides tuition fees and stipend of at least £14,777 (RCUK rate 2018/19) for UK and EU nationals that meet all required eligibility criteria.

Full eligibility details are available: View Website

Enquiries regarding programme:

References

1. Libby G et al. The Walker Project: A Longitudinal study of 48 000 children born 1952-1966 (aged 36-50 years in 2002) and their families. Paediatric & Perinatal Epidemiology 2004; 18; 302-312
2. Horikoshi et al. Genome-wide associations for birthweight and correlations with adult disease. Nature 2016; 538 (7624);248-252

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