| Title: | Dissecting the genetic basis of relationships between early-life and later-life events |
| Lead Institution: | University of Queensland |
| Principal investigator: | Professor Peter Visscher |
Application 12505
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About
Differences among individuals in distinct changes in their physiology as they age lead to differences in their susceptibility to negative later-life outcomes, and ultimately to differences in lifespan. This proposal aims to test whether genetic differences among individuals influence changes in cognition and physiological function in later life, to identify the genomic regions and biochemical pathways associated with these changes, and to test for genetic associations between early-life reproduction and later-life outcomes. This is crucial to understanding and predicting transitions across different human life stages. Understanding the genetic basis of relationships between early-life phenotypes, reproductive events, and later-life outcomes is of considerable research and public health interest. This proposal will identify new genetic relationships among physiological and cognitive functions, identify genomic regions of age-specific effect, estimate genetic relationships among life stages, and test the effects of genetic homozygosity in the genome in humans across life. It will lead to a better understanding of the genetic factors and biochemical pathways underlying cognitive and physiological decline in people as they age. Establishing robust genetic links between early and later-life health outcomes is challenging as (i) it usually requires studying people across their lives, and, when using families, (ii) relationships are confounded by other factors, such as shared environment between relatives. A novel design for studying the genetics of ageing will be used, so that even when different traits are measured on different individuals, the genetic basis of changes across life can be studied unbiased of shared environment. This enables an assessment of the genomic basis of multiple later-life phenotypes across different ages, testing theories for the genetics of ageing. For sufficient power to accurately estimate genetic relationships between characters, we require access to the full cohort. Even though individuals in the UKBiobank sample are measured across different ages, we can utilize the estimated genetic relationships among them to ask whether the genetic basis of characters is consistent across later life. We can then assess whether variation in genetic effects across life alters genetic relationships among characters throughout life (i.e., do the impacts of early-life on cognitive or physiological function only become apparent in individuals over 65). This requires data on all individuals recorded across all ages.11 Returns
| Return ID | App ID | Description | Archive Date |
|---|---|---|---|
| 3583 | 12505 | A unified framework for association and prediction from vertex-wise grey-matter structure | 22 Jun 2021 |
| 3201 | 12505 | Association Between Population Density and Genetic Risk for Schizophrenia | 11 Mar 2021 |
| 1831 | 12505 | Detection and quantification of inbreeding depression for complex traits from SNP data | 26 Nov 2019 |
| 2904 | 12505 | Dissection of genetic variation and evidence for pleiotropy in male pattern baldness | 30 Nov 2020 |
| 3365 | 12505 | Extreme inbreeding in a European ancestry sample from the contemporary UK population | 22 Apr 2021 |
| 3393 | 12505 | Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration | 29 Apr 2021 |
| 3301 | 12505 | Genotype-by-environment interactions inferred from genetic effects on phenotypic variability in the UK Biobank | 9 Apr 2021 |
| 3630 | 12505 | Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies | 9 Jul 2021 |
| 3255 | 12505 | Improved polygenic prediction by Bayesian multiple regression on summary statistics | 26 Mar 2021 |
| 3447 | 12505 | The effect of X-linked dosage compensation on complex trait variation | 25 May 2021 |
| 3672 | 12505 | Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations | 27 Jul 2021 |
41 Publications
Enabling scientific discoveries that improve human health