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Title: Genetic and environmental correlates of growth patterns leading to obesity
Author: Das, Shikta
ISNI:       0000 0005 0733 5791
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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The intrauterine period is a vulnerable period of development. Any adverse environment can permanently change the body's organ structure and function, expressed as an increased disease risk later in life. Studies show that variability in growth patterns in early life is associated with obesity and other cardiovascular diseases in adulthood, but the genetic and environmental determinants of these processes are largely unknown. The main objectives of this study were to identify genetic and environmental pre- and postnatal factors associated with early growth in infancy and childhood and later metabolic outcomes in adulthood from the Northern Finland Birth Cohorts (NFBCs). Several maternal and paternal factors, such as height, smoking, parity and pre-eclampsia, had direct association with faster postnatal height growth, some of which had their association mediated by size-at-birth variables. It was observed that an obesogenic environment in utero and during a child's growth exerts a 'programming' effect on the glucose-insulin axis as well as other cardio-vascular risk factors in adolescence. Moreover, the study shows that Leukocyte Telomere Length (LTL) at 31 years, a marker for aging, is inversely associated with multiple measures of adiposity in both men and women, and that a BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31. Two new genetic variants in/near SBNO1 and HMGA2 genes are associated with infant head circumference, which may indicate influence of brain growth and neurodevelopment via early life. Variants in/near LEPR-LEPROT, FTO, TFAP2B and GNPDA2 showed an age-dependent association with adiposity in early childhood, while three loci (FTO, TFAP2B and GNPDA2) had their effect on adult adiposity mediated by early growth phenotypes. This study emphasises the clinical importance of early growth markers as they may inform public health policy aimed at improving the pre-pregnancy environment and to monitor childhood growth during the first few years of development.
Supervisor: Jarvelin, Marjo-Riitta; Coin, Lachlan; O'Reilly, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral