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 2024:
PhD student Hanan presented some of her results at the International Mendelian Randomization conference in Bristol.
We continued our collaborative efforts within the the early growth genetics (EGG) consortium as well as the Genetics of Diabetes in Pregnancy (GenDiP) consortium. Some of the preliminary results from GenDiP was presented at the Genemappers conference in New Zealand by PhD student Caroline (University of Queensland).
Gunn-Helen also presented at the International Congress of Psychiatric Genetics in Singapore.
Co-investigators/participants:
Hanan Musa (PhD student)
External collaborators
David Evans (University of Queensland)
Caroline Brito Nunes (PhD student, University of Queensland)
Ben Brumpton (NTNU)
Bjørn Olav Åsvold (NTNU)
Deborah Lawlor (University of Bristol)
Publications from 2024
Hwang LD, Cuellar-Partida G, Yengo L, Zeng J, Toivonen J, Arvas M, Beaumont RN, Freathy RM, Moen GH, Warrington NM, Evans DM. DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits. Nat Commun. 2024 Oct 26;15(1):9255. doi: 10.1038/s41467-024-53495-9. PMID: 39461952; PMCID: PMC11513127.
D'Urso S, Wootton RE, Ask H, Brito Nunes C, Andreassen OA, Hwang LD, Moen GH, Evans DM, Havdahl A. Mendelian randomization analysis of maternal coffee consumption during pregnancy on offspring neurodevelopmental difficulties in the Norwegian Mother, Father and Child Cohort Study (MoBa). Psychol Med. 2024 Oct 9;54(12):1-14. doi: 10.1017/S0033291724002216. Epub ahead of print. PMID: 39382486; PMCID: PMC11496242.
Sidorenko J, Couvy-Duchesne B, Kemper KE, Moen GH, […], Cesarini D, Evans DM, Goddard ME, Haley CS, Porteous D, Medland SE, Martin NG, Snieder H, Metspalu A, Hveem K, Brumpton B, Visscher PM, Yengo L. Genetic architecture reconciles linkage and association studies of complex traits. Nat Genet. 2024 Oct 7. doi: 10.1038/s41588-024-01940-2. Epub ahead of print. PMID: 39375568.
Brito Nunes C, Borges MC, Freathy RM, Lawlor DA, Qvigstad E, Evans DM, Moen GH. Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy. Metabolites. 2024 Sep 20;14(9):508. doi: 10.3390/metabo14090508. PMID: 39330515; PMCID: PMC11434570.
——————————————————————————————————————————————————————————————————————————-
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.