Genetic and life course determinants of cardiovascular risk factors:structural equation modelling of complex relations

• Main Author: Kaakinen, M. (Marika)
• Other Authors: Järvelin, M. (Marjo-Riitta), Läärä, E. (Esa)
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Oulun yliopisto 2013
• Subjects: blood pressure; body mass index; cardiovascular diseases; epidemiologic methods; genes; longitudinal studies; risk factors; smoking; epidemiologiset menetelmät; geenit; painoindeksi; pitkittäistutkimukset; riskitekijät; sydän- ja verisuonitaudit; tupakointi; verenpaine; Northern Finland
• Online Access: http://urn.fi/urn:isbn:9789526200569

Abstract Cardiovascular disease is currently the leading cause of mortality worldwide. Several factors contribute to its development, including increased body mass index, high blood pressure and smoking. Many genetic and behavioural determinants of these risk factors have been identified, but the interplay between them along the life course is still poorly understood. Life course epidemiology and statistical methods developed for life course studies are required to enhance understanding of the aetiologies of these risk factors for more effective prevention and treatment of cardiovascular disease. In this thesis, structural equation modelling was applied 1) to estimate the effect of variation in the fat mass and obesity-associated gene, FTO, on body mass index over the life course, 2) to identify sensitive periods of growth in influencing adult blood pressure and 3) to identify developmental changes in the effects of two confirmed genetic loci, TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4, affecting smoking behaviour. Additionally, pleiotropic effects of the variation in CHRNA5-CHRNA3-CHRNB4 on smoking, body mass index and blood pressure were studied. The study population was based on the Northern Finland Birth Cohort 1966 with data available from early gestation until the age of 31 years (N≈6000). The first study indicated that the effect of the FTO variant on body mass index changes over time, with strengthening of the effect by age. The results from the second study demonstrated the important role of both prenatal and postnatal growth in determining adult blood pressure. In the third study, TTC12-ANKK1-DRD2 was shown to influence the initiation of smoking, while CHRNA5-CHRNA3-CHRNB4 was associated with smoking persistence. Finally, some evidence was found for pleiotropic effects of the CHRNA5-CHRNA3-CHRNB4 gene cluster on the three traits of interest. Results from all the studies emphasised the importance of environmental and behavioural factors in determining adult metabolic profile, in addition to genetic ...