Genometric Analysis of Quantitative Traits

数量性状的基因组分析

• 批准号: 6989011
• 负责人: alexander f wilson
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6989011
• 关键词: Asians; Hawaiian; Japanese American; Mennonite; age difference; alcoholic beverage consumption; cardiovascular disorder; clinical research; family genetics; gender difference; genetic markers; genetic susceptibility; genotype; human subject; noninsulin dependent diabetes mellitus; obesity; phenotype; questionnaires; smoking; statistics /biometry; tobacco abuse

This project now replaces projects HG000103, HG000128, HG000201, HG000202, HG000204, HG000205, HG000307 and HG000308. Although each of these original projects focused on different quantitative traits (e.g., obesity, diabetes, asthma, CLSD) all were applications of statistical genetic analysis of quantitative traits. All of the original projects involved linkage and/or tests of association in an attempt to identify genetic components that may be, at least in part, responsible for the variation seen in the trait. Obesity As part of an ongoing study of traits related to obesity in the Old-Order Amish, seven two- and three-generation families were assessed for twenty-one obesity related traits and genotyped. Linkage analysis and intra-familial tests of association strongly suggest a candidate region flanked by markers D7S1804 and D7S3070 for BMI. This region contains a large proportion of genes related to olfactory and taste receptors. Cardiovascular Disease The data consist of 717 observations (87 pedigrees) from Korea. The families were ascertained through probands undergoing elective coronary arteriography as part of the Yonsei Coronary Artery Disease Study. Age, sex, cigarette smoking, alcohol consumption among others covariates were obtained through a questionnaire. The following traits were measured: BMI levels of hemostatic factors (clotting factors VII and fibrinogen and plasminogen activator inhibitor ? 1 or PAI-1), triglycerides, total and HDL cholesterol, and blood pressure. The individual and family identification numbers were randomized before analysis to respect confidentiality. The Regression of Offspring on Mid-Parent (ROMP) method was used to estimate overall trait heritability and locus-specific heritability, and to test for association between the traits and the candidate polymorphisms. Although significant associations were found, these polymorphisms account for only a small percentage of the heritability of the traits (3-7%). This suggests that several other genes and/or shared familial and environmental factors may be responsible for the high heritability of these traits. Diabetes Type 2 diabetes or NIDDM is a multifactorial disorder affecting an estimated 8.6 million Americans over age 60. Dr. Richard Havlik (NIA) and other collaborators provided genetic marker data from these potential candidate regions, in an independent sample comprising 175 Japanese-American families from the Hawaiian population with a high prevalence of diabetes. Evidence of both linkage and association was obtained in the candidate region on chromosome 14, constituting independent replication of previous results in this region. These results provide additional support for the hypothesis that a susceptibility locus for Type 2 diabetes may reside in this candidate region on chromosome 14. Statistical analyses of DNA markers in this candidate region using the expression level of adiponectin, a protein related to obesity and type-2 diabetes, has been completed.

该项目现在取代项目HG 000103、HG 000128、HG 000201、HG 000202、HG 000204、HG 000205、HG 000307和HG 000308。虽然这些原始项目中的每一个都专注于不同的数量性状（例如，肥胖、糖尿病、哮喘、CLSD）都是数量性状的统计遗传分析的应用。所有最初的项目都涉及连锁和/或关联测试，试图识别可能至少部分导致性状变异的遗传成分。 肥胖 作为一项正在进行的研究的一部分，在旧秩序阿米什人的肥胖相关的性状，七个两代和三代家庭进行了评估的21个肥胖相关的性状和基因型。连锁分析和关联的家族内测试强烈建议候选区域两侧的标记D 7S 1804和D 7S 3070的BMI。该区域包含大部分与嗅觉和味觉受体相关的基因。 心血管疾病 数据包括来自韩国的717个观察结果（87个家系）。作为延世冠状动脉疾病研究的一部分，通过接受选择性冠状动脉造影的先证者确定了这些家族。通过问卷调查获得年龄、性别、吸烟、饮酒等协变量。测量以下特征：止血因子（凝血因子VII和纤维蛋白原和纤溶酶原激活物抑制剂）的BMI水平？1或派-1）、甘油三酯、总胆固醇和HDL胆固醇以及血压。在分析之前，为了保密，对个人和家庭的识别号进行了随机化。后代对中亲的回归（ROMP）方法被用来估计总体性状遗传力和位点特异性遗传力，并测试性状和候选多态性之间的关联。虽然发现了显著的关联，但这些多态性仅占性状遗传力的一小部分（3-7%）。这表明，其他几个基因和/或共享的家庭和环境因素可能是负责这些性状的高遗传性。 糖尿病 2型糖尿病或NIDDM是一种多因素疾病，影响估计860万60岁以上的美国人。Richard Havlik博士（NIA）和其他合作者提供了来自这些潜在候选区域的遗传标记数据，该数据来自一个独立样本，该样本包括来自夏威夷人口的175个日裔美国人家庭，这些家庭糖尿病患病率很高。在14号染色体上的候选区域获得了连锁和关联的证据，构成了先前在该区域的结果的独立复制。这些结果为2型糖尿病易感基因可能位于14号染色体上的这一候选区域的假设提供了额外的支持。已经完成了使用脂联素（一种与肥胖和2型糖尿病相关的蛋白质）的表达水平对该候选区域中的DNA标记物进行的统计分析。