Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966
Genome-wide association studies (GWAS) have recently shown their potential in the discovery of genetic factors associated with common diseases. Genetic association studies including GWAS can be used to explore the role of genetic variation underlying the associations between birth size, growth and m...
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Imperial College London
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ftimperialcol:oai:spiral.imperial.ac.uk:10044/1/6396 2023-05-15T17:42:26+02:00 Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966 Sovio, Ulla Maarit Hannele Järvelin, Marjo-Riitta Whittaker, John Molitor, John Medical Research Council 2011-03 http://hdl.handle.net/10044/1/6396 https://doi.org/10.25560/6396 eng eng Imperial College London Epidemiology and Biostatistics Thesis or dissertation Doctoral Doctor of Philosophy (PhD) 2011 ftimperialcol https://doi.org/10.25560/6396 2019-11-14T23:38:02Z Genome-wide association studies (GWAS) have recently shown their potential in the discovery of genetic factors associated with common diseases. Genetic association studies including GWAS can be used to explore the role of genetic variation underlying the associations between birth size, growth and metabolic phenotypes such as adiposity, lipid and glucose levels and hypertension. The aim of this thesis was to 1) review methods for genetic association analyses, 2) fit models for growth measurements, and to investigate prenatal predictors of early growth and associations between early growth and adult metabolic phenotypes, and 3) to examine genetic variation underlying birth size, postnatal growth and adult metabolic phenotypes. The primary study population comprised Northern Finland Birth Cohort 1966 (NFBC1966) members with DNA (N=5,753). Phenotypes included height/weight throughout childhood and adult metabolic phenotypes. Parametric growth curves were fitted to obtain peak growth velocities and timings of peaks and nadirs. These growth parameters were analysed in relation to birth and adult metabolic phenotypes and genetic variation. Meta-analyses of GWAS included samples with similar data. Shorter babies grew faster in length immediately after birth. Faster postnatal growth was associated with higher adult blood pressure and adiposity, independently of birth weight. Risk alleles at type 2 diabetes locus (ADCY5) were inversely associated with birth weight in a GWAS meta-analysis. Variants near BMI candidate genes LEPR and PCSK1 were associated with infant BMI. The established obesity locus (FTO) had a strong association with BMI after age 5 years. A GWAS meta-analysis of metabolic phenotypes suggested distinct pathways leading to the development of a metabolic syndrome. Adult height variants were associated with infant and/or pubertal height growth. The results suggest that foetal programming, growth acceleration and genetic susceptibility contribute to the associations between growth and metabolic phenotypes, and that some of the genetic effects are age-dependent. Doctoral or Postdoctoral Thesis Northern Finland Imperial College London: Spiral |
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Imperial College London: Spiral |
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English |
description |
Genome-wide association studies (GWAS) have recently shown their potential in the discovery of genetic factors associated with common diseases. Genetic association studies including GWAS can be used to explore the role of genetic variation underlying the associations between birth size, growth and metabolic phenotypes such as adiposity, lipid and glucose levels and hypertension. The aim of this thesis was to 1) review methods for genetic association analyses, 2) fit models for growth measurements, and to investigate prenatal predictors of early growth and associations between early growth and adult metabolic phenotypes, and 3) to examine genetic variation underlying birth size, postnatal growth and adult metabolic phenotypes. The primary study population comprised Northern Finland Birth Cohort 1966 (NFBC1966) members with DNA (N=5,753). Phenotypes included height/weight throughout childhood and adult metabolic phenotypes. Parametric growth curves were fitted to obtain peak growth velocities and timings of peaks and nadirs. These growth parameters were analysed in relation to birth and adult metabolic phenotypes and genetic variation. Meta-analyses of GWAS included samples with similar data. Shorter babies grew faster in length immediately after birth. Faster postnatal growth was associated with higher adult blood pressure and adiposity, independently of birth weight. Risk alleles at type 2 diabetes locus (ADCY5) were inversely associated with birth weight in a GWAS meta-analysis. Variants near BMI candidate genes LEPR and PCSK1 were associated with infant BMI. The established obesity locus (FTO) had a strong association with BMI after age 5 years. A GWAS meta-analysis of metabolic phenotypes suggested distinct pathways leading to the development of a metabolic syndrome. Adult height variants were associated with infant and/or pubertal height growth. The results suggest that foetal programming, growth acceleration and genetic susceptibility contribute to the associations between growth and metabolic phenotypes, and that some of the genetic effects are age-dependent. |
author2 |
Järvelin, Marjo-Riitta Whittaker, John Molitor, John Medical Research Council |
format |
Doctoral or Postdoctoral Thesis |
author |
Sovio, Ulla Maarit Hannele |
spellingShingle |
Sovio, Ulla Maarit Hannele Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966 |
author_facet |
Sovio, Ulla Maarit Hannele |
author_sort |
Sovio, Ulla Maarit Hannele |
title |
Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966 |
title_short |
Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966 |
title_full |
Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966 |
title_fullStr |
Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966 |
title_full_unstemmed |
Genetic variation, growth and metabolic phenotypes in the longitudinal Northern Finland Birth Cohort 1966 |
title_sort |
genetic variation, growth and metabolic phenotypes in the longitudinal northern finland birth cohort 1966 |
publisher |
Imperial College London |
publishDate |
2011 |
url |
http://hdl.handle.net/10044/1/6396 https://doi.org/10.25560/6396 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_doi |
https://doi.org/10.25560/6396 |
_version_ |
1766144284886564864 |