Dr Rachel Freathy
Sir Henry Dale Fellow and Senior Research Fellow
Endocrinology and Metabolism
Institute of Biomedical and Clinical Science, University of Exeter Medical School
Skills Development Fellowship Vision
For me, a successful Skills Development Fellowship will start with an enthusiastic and energetic researcher with a strong background in informatics and a passion for developing those skills in relation to a clear biomedical or clinical research question (or vice versa). The fellow will be supported by sponsors with complementary expertise, access to excellent resources and a stimulating research environment with plenty of opportunity for interaction both within the institution and with external collaborators. With this support network, they will be able to direct and develop their own research programme, and over the three years, gain an increasing level of independence as they carve out their own niche at the interface between the quantitative and biomedical disciplines. At the end of the fellowship they will be in an excellent position to apply for an independent academic position and to begin their own research group.
I gained my BA in Biological Sciences from the University of Oxford and completed a Masters in Biological Research Methods at the University of Exeter, before completing my PhD in molecular genetics of type 2 diabetes and body size, also in Exeter. I was then awarded a Sir Henry Wellcome Postdoctoral Fellowship to research the links between the genetics of type 2 diabetes and fetal growth, which enabled me to spend time at the University of Bristol and Northwestern University in Chicago, as well as continuing in Exeter. In 2014, I was awarded a Sir Henry Dale Fellowship to begin my own research group here in Exeter, using genetics to understand maternal and fetal influences on birth weight.
I am interested in using large genetics datasets to understand both genetic and non-genetic (maternal intrauterine) influences on birth weight. The techniques used could be applied to many outcomes other than birth weight, including later life diseases.
Techniques include (i) genome-wide association studies (GWAS) to identify genetic loci of relevance to a human trait/disease; (ii) Mendelian randomization to understand causal relationships between maternal exposures and offspring outcomes; (iii) use of mother-child pairs/parent-offspring trios to understand parent-of-origin effects and maternal intrauterine effects.
Datasets include (i) the UK Biobank, an outstanding resource of genome-wide genetic data on 500,000 UK participants and a rich variety of phenotypes; (ii) the ALSPAC, EFSOCH and HAPO studies: three studies of mothers and babies (total N > 20,000) with a wealth of genetics, pregnancy, birth and childhood data; (iii) summary data from collaborating studies within the Early Growth Genetics (EGG) Consortium (>100,000 mothers or babies in sets of results from meta-analyses).
Genome-wide associations for birth weight and correlations with adult disease. Horikoshi M, Beaumont RN, Day FR, Warrington NM, Kooijman MN, [155 coauthors], Timpson NJ, Perry JR, Evans DM, McCarthy MI, Freathy RM. Nature. 2016 Oct 13;538(7624):248-252. doi: 10.1038/nature19806. PMID: 27680694; PMCID: 5164934.
My contribution: Co-designed the study and co-led the analysis and writing of the paper. In this paper, we described 60 birth weight-associated loci identified through GWAS, 53 of which are newly-identified. We demonstrated genome-wide genetic correlations between birth weight and several adult diseases and traits, and provided initial estimates that a large proportion of the overall covariance between birth weight and type 2 diabetes or blood pressure is due to shared genetic factors. URL: http://rdcu.be/k12A
Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight. Tyrrell J, Richmond RC, Palmer TM, Feenstra B, Rangarajan J, [53 coauthors], Hyppönen E, Lowe WL Jr, Frayling TM, Lawlor DA, Freathy RM for the Early Growth Genetics (EGG) Consortium. JAMA. 2016 Mar 15;315(11):1129-40. doi: 10.1001/jama.2016.1975. PMID: 26978208; PMCID: 4811305.
My contribution: Co-designed the study and co-led the analysis and writing of the paper. In this study, we used Mendelian randomization to demonstrate evidence of causal associations between higher maternal BMI or glucose and higher offspring birth weight, and between higher maternal systolic blood pressure and lower offspring birth weight. We found no evidence of causal associations between maternal triglyceride, HDL-cholesterol or adiponectin levels and birth weight. Highly cited paper: as of May/June 2017, this paper received enough citations to place it in the top 1% of the academic field of Clinical Medicine (Web of Science). URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811305/
Ongoing Projects & Grants
- MRC GW4 BioMed PhD Studentship (co-I). Project: “Using genetics to understand how the maternal intrauterine environment influences fetal growth.”
- Wellcome Trust and Royal Society Sir Henry Dale Fellowship (PI): “Using genetics to understand how the maternal intrauterine environment influences fetal growth”.
Within Exeter, I work closely with the Complex Traits Genetics team led by Prof. Tim Frayling and the Genetics of Diabetes clinical team led by Prof. Andrew Hattersley.
Outside Exeter, I have strong collaborative links with Prof. Debbie Lawlor and Prof. George Davey Smith at the University of Bristol, who have expertise in epidemiological techniques, in particular Mendelian randomization. I also collaborate closely with Prof. Bill Lowe at Northwestern University Chicago, PI of the Hyperglycemia and Adverse Pregnancy Outcome study.
Finally, I am a leading member of the international Early Growth Genetics (EGG) Consortium, a collaboration of researchers representing >40 studies, with interests in genetics and early growth phenotypes.
Research Group Connections