Genetic analyses of dynamic quantitative traits

This dissertation presents a research strategy for identifying new cardiovascular disease susceptibility genes that takes advantage of information in measures of the dynamics of blood pressure (BP) rather than measures of the statics. Five primary questions were addressed. The first question is whether ambulatory BP measurements (ABPM) have non-random patterns. The second question is whether traits that measure the non-random patterns in ABPM (termed dynamic traits) are different measures of BP regulation than the mean. The third question is whether dynamic traits are influenced by measures of an individual's biology and/or environment. The fourth question is whether dynamic traits are predictive of an individual's risk of essential hypertension. The fifth question is whether dynamic traits improve our ability to identify and characterize genes that influence BP regulation beyond that provided by traits that measure static features of ABPM (termed static traits).; We obtained systolic and diastolic ABPM every 10 minutes over a 24-hour period in 199 healthy non-Hispanic whites (84 females, 115 males) from Rochester, MN. The mean and standard deviation were selected as static traits while the autocorrelation function (ACF) and grammar complexity statistic were selected as linear and nonlinear dynamic traits of ABPM respectively. We measured the M235T and the –6A/G polymorphisms in the angiotensinogen (AGT) gene, the A/C1166 polymorphism in the angiotensin II receptor type 1 (AT1) gene, the I/D polymorphism in the angiotensin converting enzyme (ACE) gene and the (ACAG)n polymorphism in the renin ( REN) gene.; From the results of this dissertation we conclude that (1) ABPM have non-random patterns, (2) dynamic traits are different measures of BP regulation than the mean, (3) dynamic traits are influenced by measures of an individual's biology and/or environment, (4) dynamic traits are predictive of an individual's risk of essential hypertension and (5) dynamic traits improve our ability to identify genes that influence BP regulation beyond that provided by just static traits. It is expected that the findings of this dissertation will alter the current paradigm for studying the genetics and epidemiology of BP regulation and essential hypertension in clinical and experimental settings.