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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Developing and Applying New Statistical Models to Test for Transgenerational Effects of Environmental Exposures in Pregnancy

Alternative title: Utvikling og bruk av nye statistiske modeller for å teste effekten av miljøeksponering under graviditet på fremtidige generasjoner

Awarded: NOK 10.0 mill.

Women from poorer backgrounds are more likely to have infants who are born preterm (prematurely) and have low birth weight. Previous research shows this might be because of poorer diets and women from poorer backgrounds being more likely to smoke or drink alcohol during pregnancy. More controversially, researchers have also shown links between these adverse environmental exposures during pregnancy and the long-term health of future generations (i.e. the children’s children). However, since these correlations cannot be investigated by randomized controlled trials (as it would be both unethical to subject pregnant women and their children to harmful exposures and expensive and time consuming to follow the individuals across at least one generation), it is unclear whether these transgenerational associations represent causal relationships. Indeed, without a method to investigate transgenerational effects robustly, the scientific community cannot prove whether they exist, and if so, the true extent of their biological, medical and economic importance. We will develop and apply three novel statistical methods to test for the existence of transgenerational inheritance of environmental exposures in human populations, as an alternative to conducting Randomized Controlled Trials. The project will provide strong evidence for or against the existence of transgenerational effects in humans. We will deliver new knowledge regarding transgenerational biological mechanisms, as well as adaptation to unfavourable environmental exposures and the subsequent health of future generations.

This project will develop causal models and methods that will have widespread applicability to questions related to transgenerational inheritance in humans. The project will provide strong evidence for or against the existence of transgenerational effects on birthweight that will yield new knowledge regarding transgenerational biological mechanisms, adaptation to unfavourable environmental exposures and the subsequent health of future generations. This is important because 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. Ideally, strong evidence for the existence of transgenerational effects in humans could be obtained from Randomized Controlled Trials. However, Randomized Controlled Trials cannot be performed easily in this context and in most cases would be unethical. Without a method to investigate transgenerational effects robustly, the scientific community cannot prove whether they exist in humans, nor evaluate the true extent of their biological, medical and economic importance. We will 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. We will focus on grandchild’s birthweight as a model phenotype to test for the existence of these transgenerational effects because (a) such effects, if they exist, are likely to manifest most strongly in the case of perinatal phenotypes; and (b) there are large genotyped cohorts, which we can access, with information on three generations of individuals and birthweight with considerable statistical power to detect such effects.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

Funding Sources