Genometric Analysis of Quantitative Traits

该项目现在取代了项目HG000103、HG000128、HG000201、HG000202、HG000204、HG000205、HG000307和HG000308。虽然这些原始项目中的每一个都侧重于不同的数量性状(例如肥胖、糖尿病、哮喘、慢性阻塞性肺病)，但都是对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，以试图确定可能至少部分导致性状变异的遗传成分。 肥胖 作为正在进行的旧秩序阿米什人肥胖相关特征研究的一部分，七个两代和三代家庭被评估了21个肥胖相关特征并进行了基因分型。连锁分析和家系内关联检验强烈建议BMI的候选区域由标记D7S1804和D7S3070组成。这个区域包含很大比例的与嗅觉和味觉感受器相关的基因。 心血管疾病 数据包括来自韩国的717个观测数据(87个家系)。这些家庭是通过接受选择性冠状动脉造影术的先证者确定的，这是延世冠状动脉疾病研究的一部分。通过问卷调查获得年龄、性别、吸烟、饮酒等协变量。测量以下指标：止血因子(凝血因子VII、纤维蛋白原和纤溶酶原激活物抑制物1或PAI-1)的BMI水平、甘油三酯、总胆固醇和高密度脂蛋白，以及血压。为了尊重保密性，在分析之前，个人和家庭的身份号码是随机的。采用中亲子代回归(ROMP)方法估计总遗传力和座位特异性遗传力，并检验这些性状与候选多态之间的关联性。虽然发现了显著的相关性，但这些多态只占性状遗传力的一小部分(3-7%)。这表明，其他几个基因和/或共同的家族和环境因素可能是这些性状的高遗传力的原因。 糖尿病 2型糖尿病或NIDDM是一种多因素疾病，估计有860万60岁以上的美国人受到影响。理查德·哈夫利克博士(NIA)和其他合作者在一个独立样本中提供了来自这些潜在候选区域的遗传标记数据，样本包括175个来自糖尿病高发人群的夏威夷日裔美国家庭。在14号染色体上的候选区域获得了连锁和关联的证据，构成了该区域先前结果的独立复制。这些结果进一步支持了这一假设，即2型糖尿病的易感基因可能位于14号染色体上的这个候选区域。利用与肥胖和2型糖尿病相关的蛋白质脂联素的表达水平对该候选区域的DNA标记进行了统计分析。

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.