We aim to utilize the Northern Finland Birth Cohort 1966 (NFBC1966) to identify sequence variants associated with quantitative traits that are important risk factors for cardiovascular disease and the metabolic syndrome. The NFBC is drawn from a population that combines a significant founder effect and subsequent isolation with a Western life style and comprehensive health care system with excellent registers. This cohort is ideally suited for investigating a) genetic risk factors underlying a wide spectrum of cardiovascular diseases, and b) the relationship between DMA variants and well defined environmental and life style variables. In particular, this longitudinal study has prospectively collected details of early life events, thought to be critical risk factors for many cardiovascular diseases. We hypothesize that allelic variations in several genes are responsible for the genetic component of the variance for several quantitative traits relevant to cardiovascular disease. Some of these variants are likely to be responsible predominantly for threshold effects, while others are likely to have a truly quantitative effect on the trait. We further hypothesize that it is highly advantageous to search for these variants in a setting with a restricted number of ancestral disease alleles, as are expected to be found in study samples in NFBC. While the current proposal focuses on a small number of well characterized phenotypes, once the genotypes have been obtained, it will be possible to use the wealth of phenotypic data available to conduct similar analyses for a large number of other traits related to heart, lung and blood disorders. Specifically we aim: 1) To conduct a whole genome association (WGA) study for quantitative traits relevant to cardiovascular risk in 2000 individuals from NFBC1966, 2) To perform statistical analyses to investigate the relationships between gene variants and between genetic variants and lifestyle/ environmental risk factors, focusing particularly on early life events. 3) To use the remainder of NFBC1966 (about 3900 individuals) for extension and finer-scale association analyses of significant association signals identified in aims 1 and 2.
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