Genetics of cardiovascular risk factors in large founder population birth control

描述(由申请人提供)： 我们的目标是利用芬兰北部出生队列1966(NFBC1966)来识别与数量性状相关的序列变异，这些数量性状是心血管疾病和代谢综合征的重要风险因素。NFBC来自一群人，他们结合了显著的创始人效应和随后的与世隔绝，以及西式生活方式和全面的医疗保健系统以及出色的登记。该队列非常适合于研究a)导致广泛心血管疾病的遗传风险因素，以及b)DMA变异与明确定义的环境和生活方式变量之间的关系。特别是，这项纵向研究前瞻性地收集了早期生活事件的细节，这些事件被认为是许多心血管疾病的关键风险因素。我们假设，几个基因的等位基因变异是与心血管疾病相关的几个数量性状变异的遗传成分。这些变异中的一些可能是阈值效应的主要原因，而另一些可能对性状产生真正的数量效应。我们进一步假设，在祖先疾病等位基因数量有限的情况下搜索这些变异是非常有利的，正如预计在NFBC的研究样本中发现的那样。虽然目前的建议侧重于少数具有良好特征的表型，但一旦获得了表型，就有可能利用丰富的表型数据对与心、肺和血液疾病有关的大量其他特征进行类似的分析。具体地说，我们的目标是：1)对NFBC1966的2000名个体进行与心血管风险相关的数量性状的全基因组关联(WGA)研究；2)进行统计分析，以调查基因变异之间以及遗传变异与生活方式/环境风险因素之间的关系，特别是早期生活事件。3)使用NFBC1966的剩余部分(约3900个个体)对目标1和2中确定的显著关联信号进行扩展和更精细的关联分析。

DESCRIPTION (provided by applicant): 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. (End of Abstract)