The Advanced Pedigree: Predicting Childhood Obesity Risk Utilizing a Pluralistic Model of Heredity
Abstract
This dissertation examines the use of the pedigree in healthcare and applies the pluralistic model of heredity to both genetic and non-genetic (epigenetic) changes that lead to disease to identify some of the “missing heritability” in childhood obesity. This dissertation provides an original childhood obesity model drafted from the literature review, quantitatively describing the genetic and non-genetic influences on the growth of a child for use in the pluralistic model of heredity to determine the risk of obesity. The pedigree analysis describes how to identify genetic diseases such as obesity or Marfan Syndrome in a family pedigree. Marfan Syndrome is used as an example of a single genetic mutation influencing the growth of affected children in contrast to the multifactorial etiology of childhood obesity. The research findings in this dissertation assess the growth of 18 month old children in a cohort of Australian twins, examining associations between infant nutrition (non-genetic environmental influence) and childhood growth. While sample size was small (n=179), the analysis suggested that infants breastfed for 1-3 months were significantly larger than infants breastfed for 4-6 months in terms of mean BMI (0.61 kg/m2; P=0.02; 95% CI: 0.17-1.05), arm circumference (0.66 cm; P=0.006; 95% CI: 0.26-1.06) and abdominal circumference (1.16 cm; P=0.03; 95% CI: 0.26-2.06). Duration of breastfeeding had a significant phenotypic variation in growth in children enrolled in the PETS (Peri/postnatal Epigenetic Twins Study). Breastfeeding for 4-6 months appeared to protect against the risk of obesity. This pilot study is the foundation for future research analyzing methylation data for investigating potential epigenetic mechanisms for childhood obesity. Lastly, I propose the expansion of a statistical method in quantitative genetics with the inclusion of a pluralistic model of heredity, using an advanced pedigree for assessing the risk of childhood obesity. This unique statistical method in quantitative genetics, utilizes genetic and non-genetic components in a pluralistic model of heredity entitled the “Advanced Pedigree”. The advanced pedigree model can guide future epigenetic research and calculate both genetic and environmental risk for developing complex multifactorial diseases such as obesity. Additional research is needed to examine the validity of the statistical method.