B4034 - Using genetics to understand causal mechanisms underlying pregnancy outcomes for mothers and babies - 21/04/2022

B number: 
Principal applicant name: 
Rachel Freathy | University of Exeter (UK)
Miss. Annika Jaitner, Prof. Jack Bowden, Prof. Krasimira Tsaneva-Atanasova
Title of project: 
Using genetics to understand causal mechanisms underlying pregnancy outcomes for mothers and babies
Proposal summary: 

**Please note that this project is linked to our existing B3392 project and will mostly require variables that we already have in Exeter in the B3392 dataset.**
References to previously published work in the summary below are given as PubMed IDs.

Maternal smoking during pregnancy is associated with various adverse pregnancy outcomes. Despite a strong public health message, many pregnant women continue to smoke. Studies and data analysis indicate that maternal smoking is associated with a reduction in offspring birth weight (PMID: 33173933 and PMID: 22956269), which is likely to be due to an adverse effect of smoking on placental function. Placental weight is often used as a convenient indicator of placental function (PMID: 32421535). However, information on the effect of smoking during pregnancy on placental weight is limited. The literature reports both lower and higher placental weights for women who smoked during pregnancy, relative to those who did not smoke (PMID: 32421535 and PMID: 29947760). We aim to gain a better understanding of the risk of smoking during pregnancy by using genetics to test whether smoking is causally related to placental weight, and to better understand the underlying mechanisms connecting smoking, placental weight and birth weight. So far, the team in Exeter have used ALSPAC and other studies to identify genetic variations in both mothers and babies that are associated with birth weight (PMID: 31043758), to show that genetic variation influences how likely women are to quit smoking in pregnancy (PMID: 19429911), and to show that this same genetic variation influences birth weight via its effect on smoking (PMID: 22956269). The current project will build on those findings and relate smoking, birth weight and placental weight.

Impact of research: 
High impact publications improving understanding of mechanisms of how smoking relates to fetoplacental growth in human pregnancy. New tools and methods for causal mediation and MR analysis of family data, that can be applied more widely by researchers in the field.
Date proposal received: 
Tuesday, 29 March, 2022
Date proposal approved: 
Thursday, 21 April, 2022
Genetic epidemiology (including association studies and mendelian randomisation), Addiction - e.g. alcohol, illicit drugs, smoking, gambling, etc., Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, GWAS, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods, Epigenetics, Fathers, Genetic epidemiology, Genetics, Genome wide association study, Growth, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics