Genome-Wide Predictors of Plasma Folate and Homocysteine

血浆叶酸和同型半胱氨酸的全基因组预测因子

• 批准号: 7689156
• 负责人: Aditi Hazra
• 金额: $ 8.18万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-19 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7689156
• 关键词: Accounting; Alcohol consumption; Blood; Breast; Candidate Disease Gene; Carbon; Caucasians; Caucasoid Race; Chronic Disease; Classification; Colorectal Adenoma; Colorectal Cancer; Consumption; Custom; DNA; DNA Methylation; Data; Development; Epidemiologic Studies; Evaluation; Folate; Folic Acid; Folic Acid Deficiency; Funding; Future; Genes; Genetic; Genetic Markers; Genetic Variation; Genotype; Haplotypes; Heart Diseases; Heritability; Homocysteine; Homocystine; Individual; Inherited; Intake; Investigation; Malignant Neoplasms; Measures; Meta-Analysis; Metabolic; Metabolism; National Cancer Institute; National Heart, Lung, and Blood Institute; Nested Case-Control Study; Nutrient; Nutritional; Pancreas; Participant; Pathway interactions; Plasma; Population; Postmenopause; Predisposition; Prevention strategy; Prospective Studies; Prostate; Purines; Reaction; Research; Research Personnel; Resources; Risk; Scanning; Staging; Structure; Subgroup; Supplementation; Testing; Uracil; Variant; Vitamin B 12; Vitamin B Complex; Vitamin B6; Water; Woman; absorption; adenoma; alcohol measurement; base; cancer genetics; cancer prevention; cancer risk; carcinogenesis; cost; design; folic acid metabolism; fortification; fruits and vegetables; genetic linkage analysis; genome wide association study; genome-wide; genome-wide analysis; insight; malignant breast neoplasm; methionine synthase reductase; novel; nutrition; prospective; purine; response; trend; vitamin metabolism

DESCRIPTION (provided by applicant): Folate and homocysteine are essential components of one-carbon metabolism. Diminished folate and increased homocysteine plasma levels are associated with colorectal cancer (CRC) and breast cancer particularly among those who consume moderate to high levels of alcohol, which interferes with one-carbon metabolism. Less than 10% of the genetic variance in the heritable levels of plasma folate and plasma homocysteine can be explained. Therefore we propose to conduct a cost-effective multistage analysis of genome-wide data on plasma folate and homocysteine levels among 1,629 women in the National Cancer Institute sponsored Cancer Genetic Markers of Susceptibility project, perform 2.5 million SNP imputations based on haplotype structure and combine these data with data from participants in the National Heart Lung and Blood Institute's Framingham SNP-Health Association Resource study. This proposal incorporates systematic association testing of common genetic variation including known associations and identifying novel pathways. We will replicate a subset of the highest-ranking SNPs from the hypotheses generated in the initial analysis in 960 women and explore the most promising SNP associations with risk of CRC and adenoma (CRA). As the first genome-wide association study of plasma folate and homocysteine, these data will provide an integrated research paradigm that synthesizes genome-wide analytic approaches and metabolic profiling to offer an informative platform for understanding gene-nutrient relationships and their potential association with CRC and CRA. Our empirical characterization of genetic variation in plasma levels of folate and homocysteine will provide insight for cancer prevention strategies and elucidate which population subgroups may benefit most from additional folate intake or supplementation due to genetic variation in B-vitamin metabolism or absorption.

描述（由申请人提供）：