Genetics of cardiovascular risk factors in large founder population birth control

大型创始人群体节育中心血管危险因素的遗传学

• 批准号: 7226490
• 负责人: LEENA PELTONEN
• 金额: $ 268.56万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226490
• 关键词: Alleles; Birth; Blood Pressure; C-reactive protein; Cardiac; Cardiovascular Diseases; Complex; Comprehensive Health Care; Custom; Data; Diastolic blood pressure; Disease; Ensure; Environment; Environmental Risk Factor; European; Event; Fasting; Female; Finland; Founder Effect; Founder Generation; Genes; Genetic; Genetic Variation; Genome; Genotype; Glucose; Haplotypes; Heart; Hematological Disease; Heritability; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Individual; Insulin; Joints; LDL Cholesterol Lipoproteins; Life; Life Style; Linkage Disequilibrium; Longitudinal Studies; Low-Density Lipoproteins; Lung; Metabolic; Metabolic syndrome; Molecular; Numbers; Participant; Pathogenesis; Pathway interactions; Persons; Phenotype; Plasma; Population; Process; Quantitative Trait Loci; Range; Research Personnel; Risk; Risk Factors; Sampling; Sampling Studies; Signal Transduction; Societies; Staging; System; Testing; Thinking; Triglycerides; Variant; abstracting; birth control; cardiovascular disorder risk; cardiovascular risk factor; cohort; follow-up; gene environment interaction; gene interaction; genetic risk factor; genetic variant; genome wide association study; indexing; interest; male; programs; sex; trait

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)

描述（由申请人提供）： 我们的目标是利用北方芬兰出生队列1966（NFBC 1966），以确定与数量性状，心血管疾病和代谢综合征的重要危险因素相关的序列变异。NFBC是从一个人口，结合了显着的创始人效应和随后的隔离与西方的生活方式和全面的医疗保健系统与优秀的注册。该队列非常适合研究a）广泛的心血管疾病的遗传风险因素，和B）DMA变体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，在几个基因的等位基因变异是负责几个数量性状相关的心血管疾病的变异的遗传成分。其中一些变异可能主要负责阈值效应，而其他变异则可能对性状产生真正的数量效应。我们进一步假设，在具有有限数量的祖先疾病等位基因的环境中搜索这些变体是非常有利的，正如预期在NFBC的研究样本中发现的那样。虽然目前的建议集中在少数良好表征的表型，一旦基因型已经获得，它将有可能使用丰富的表型数据进行类似的分析，为大量的其他性状相关的心脏，肺和血液疾病。我们的具体目标是：1）对来自NFBC 1966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，特别关注早期生活事件。3)使用NFBC 1966的剩余部分（约3900人）对目标1和目标2中确定的重要关联信号进行扩展和更精细的关联分析。(End摘要）