| Application: | 12703, Investigating the Genetic Architecture Underlying the Developmental Origins of Health and Disease |
| Title: | Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank |
| Size: | 4.0 MB |
| Archived: | 12 Feb 2020 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
Return 2002
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Notes
A mother and her child share half of their genetics in common, and both genomes will have an influence on perinatal traits such as birth weight. This sharing complicates the estimation of small genetic effects, especially when genetic data is not available on both the mother and her child. Therefore, we developed a statistical model to estimate the maternal and child genetic effects on a trait when we have genetic data on the mother and trait data on both herself and her child. We used data from the UK Biobank to estimate the effect of the maternal genetics on her childs birth weight and the childs genetics on their own birth weight. We showed that of the 58 genetic variants we investigated, several had a greater effect on birth weight when they were present in the mother. Additionally, a handful of genetic variants increased birth weight when present in the mother but decreased birth weight when present in her child. This statistical model will help us understand more about the mechanisms underlying the genetic associations with perinatal traits.Application 12703
Investigating the Genetic Architecture Underlying the Developmental Origins of Health and Disease
The prevalence of cardiovascular disease, diabetes, osteoporosis and infertility are increasing and the financial burden on society is substantial. Research has shown a link between birth weight and increased risk of these diseases and other cardiovascular/metabolic disorders. Genetics may be involved as not all individuals born of suboptimal weight go on to develop disease. The aims of this research are to: (1) identify novel genes that explain the adverse relationship between birth weight and cardiometabolic disorders, osteoporosis or infertility, (2) determine biological intermediates that partially mediate the relationship between birth weight and these disorders, using genetic profile scores. Currently, most interventions target individuals after the onset of clinical symptoms, by which time treatment is expensive and of limited effectiveness. The Developmental Origins of Health and Disease (DOHaD) paradigm suggests that there may be critical windows earlier in life that offer opportunities for disease treatment and prevention. The overall aim of this project is to use novel statistical genetics methods to identify genes that explain part of the observational association between birth weight and risk of cardiometabolic disease, osteoporosis or infertility, providing a better understanding of this relationship and its implications for future development of disease. We will conduct a genome-wide association study to identify individual genetic variants and regions of the genome that are 1) jointly associated with birth weight and cardiometabolic disorders or osteoporosis, 2) associated with fracture risk or bone related phenotypes and 3) associated with fertility defects. In addition, we will use genetic risk scores for biological characteristics to investigate whether those characteristics partially mediate the observed relationship between birth weight and subsequent risk of disease in later life. Whole cohort with genetic data that have reported their birth weight, diagnosis of cardiometabolic diseases, osteoporosis or fertility defects.
| Lead investigator: | Dr Nicole Warrington |
| Lead institution: | University of Queensland |
3 related Returns
| Return ID | App ID | Description | Archive Date |
|---|---|---|---|
| 2735 | 12703 | Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study | 2 Nov 2020 |
| 3141 | 12703 | Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis | 26 Feb 2021 |
| 2903 | 12703 | Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors | 30 Nov 2020 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 2003 | Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank | Nicole M Warrington (+3) | 2018 | International Journal of Epidemiology |
Enabling scientific discoveries that improve human health