Developing and Applying New Statistical Models to Test for Transgenerational Effects of Environmental Exposures in Pregnancy
A study of genetic factors in HUNT.
There is growing evidence suggesting that environmental exposures, such as maternal diet, alcohol consumption and smoking during pregnancy may have long-term biological consequences across multiple generations, potentially playing a role in disease susceptibility. Transgenerational effects may be defined as long term effects of environmental exposures that are transmitted down pedigrees and affect the health not only of an individual’s children, but that of subsequent generations as well (i.e., grandchildren and beyond).
The aim of this project is to develop and apply three different statistical approaches to test for the existence of transgenerational inheritance of environmental exposures in human populations, as an alternative to conducting randomized controlled trials.
The focus will specifically be on the potential causal effect of grandparental environmental exposures on their grandchildren’s birthweight.
News from 2022:
In 2022 we started this project and recruited our PhD student, Hanan Musa which started in November of 2022. We are looking forward to starting analysis in 2023!
Co-investigators/participants:
Hanan Musa (PhD student)
External collaborators
David Evans (University of Queensland)
Ben Brumpton (NTNU)
Bjørn Olav Åsvold (NTNU)
Deborah Lawlor (University of Bristol)
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Why does low birthweight increase the risk of type 2 diabetes and other cardiometabolic diseases?
A study of genetic factors in HUNT.
There is a robust and well-documented relationship between lower birthweight and higher risk of cardiometabolic disease in later life, including Type 2 Diabetes. Two major hypotheses have been put forward to explain this association. The first is the Developmental Origins of Health and Disease hypothesis (DOHaD), which posits that adverse intrauterine environments result in fetal growth restriction and increased future risk of cardiometabolic disease through developmental compensation. In contrast, the Fetal Insulin Hypothesis postulates that the same genetic factors that alter intrauterine growth also affect future risk of disease. Broadly speaking, diabetes risk alleles in the mother result in higher levels of circulating glucose - increase offspring birthweight. However, many of the same loci in the fetus decrease sensitivity to insulin (an important growth factor for the baby), decreasing offspring birthweight, which also predisposes the child to Type 2 Diabetes in later life.
By applying innovative statistical techniques to mother-offspring genome-wide association studies (GWAS) data from the Norwegian HUNT cohort, we investigate the relationship between birthweight and cardiometabolic disease.
News from 2022:
In 2022 we finished this project and published the last planed paper where we investigated the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors.