Our study, published in the journal, Nature Genetics on 1st May 2019 shows how the genetics of mother and baby shed light on links between birth weight and later health: https://go.nature.com/2vy40hv . This was a collaborative study led by researchers at the Universities of Exeter, Queensland, Oxford and Cambridge. We identified 190 associations between birth weight and specific parts of our DNA. Two-thirds of these had not been identified before, and for many of these associations, we can now say whether it s (i) direct effect of baby s genetics, or (ii) indirect effect of mother s genetics via the womb environment, or (iii) both. This is important because very small babies are at greater risk of birth complications and later-life risk factors e.g. high blood pressure (BP). Separating environmental effects of maternal genes from inherited baby effects enables us to test e.g. whether womb environment / genes / both contribute to higher later-life BP. We found that the low birth weight high BP relationship is complex, involving both genes and environment: high mother s BP causes lower birth weight, i.e. maternal environment effect. But NO evidence that mother s BW-lowering environment raises offspring BP. Rather, higher offspring BP is due to inherited genetic factors. An innovative statistical method made it possible to separate mother-baby effects in this well-powered sample. The wonderful UK Biobank and fantastic collaborations in the EGG consortium provided the power.
Understanding how maternal and fetal genetic and environmental factors influence offspring birth weight
We aim to identify genetic and environmental factors that are causally associated with birth weight. Both lower and higher birth weights in the normal range are observationally associated with a higher risk of type 2 diabetes in later life, but the causes of these associations are poorly understood.
We propose to investigate three related research questions:
(1) Which common fetal genetic variants are robustly associated with offspring birth weight?
(2) Which common maternal genetic variants are robustly associated with offspring birth weight?
(3) Which maternal intra-uterine environmental exposures are causally associated with offspring birth weight? Improving the prevention, diagnosis and treatment of diabetes:
(1) Fetal genetic variants associated with an individual?s own birth weight will highlight biological pathways relevant to fetal growth and may indicate links with pathways relevant to diabetes, enabling a better understanding of what causes the disease.
(2) Maternal genetic variants known to influence diabetes- or obesity-related traits may be used to test the hypothesis that those traits are causally associated with the birth weight of her offspring. This will improve understanding of the factors responsible for increased fetal growth and associated risks in a diabetic or obese pregnancy. We will perform
(a) [hypothesis-free] genome-wide association studies examining
(i) associations between a participant's genotype (fetal) and their own birth weight,
(ii) associations between a female participant's genotype (maternal) and the birth weight of their first child, and
(b) [hypothesis-driven] analyses of associations between maternal genetic variants known to influence traits relevant to the maternal environment (fasting glucose, blood pressure etc) and offspring birth weight. Since genetic variants are unlikely to be confounded, the latter will be a Mendelian randomization analysis to investigate causality in associations between maternal environmental factors and offspring birth weight. We propose to use the full UK Biobank cohort for the fetal genome-wide association study, while for the maternal genome-wide association study and Mendelian randomization analyses, we plan to use the subset of women with data on birth weight of first child (n=221,522).
|Lead investigator:||Dr Rachel Freathy|
|Lead institution:||University of Exeter|
3 related Returns
|Return ID||App ID||Description||Archive Date|
|2881||7036||Association of maternal circulating 25(OH)D and calcium with birth weight: A mendelian randomisation analysis||26 Nov 2020|
|1848||7036||Genome-wide association study of offspring birth weight in 86577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics||3 Dec 2019|
|752||7036||Genome-wide associations for birth weight and correlations with adult disease||17 Oct 2017|
|2904||Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors||Warrington NM et al.||2019||Nat Genet|