GENETICS OF GALLBLADDER DISEASE IN MEXICAN AMERICANS

描述：（改编自研究者摘要）胆囊疾病 (GBD)是美国发病和死亡的主要原因之一 States.在墨西哥裔美国人等人群中， GBD很高，并且经常与非胰岛素样疾病聚集在一起 依赖性糖尿病（NIDDM）和肥胖。GBD的病因是 不清楚，但据信是多因素的起源， 肝胆系统异常，如胆汁过饱和 与胆固醇，胆固醇成核的变化，以及 胆囊尽管有流行病学证据表明 与风险因素，如年龄，性别（女性较高），肥胖，本地 美国血统、NIDDM和心血管疾病危险因素， 遗传决定GBD的证据非常有限。 该项目的目的是进行遗传流行病学调查， 涉及分子遗传学数据、GBD表型和 统计遗传学技术，以检查变异的遗传基础 在一组32个低收入墨西哥裔美国家庭中， 目前正在调查有关基因测定 圣安东尼奥家庭糖尿病研究（SAFADS）。整体 本研究的目的是测量对GBD表型的遗传效应， 并鉴定和定位GBD易感基因。具体目标 是1）定义GBD表型，例如胆结石疾病（存在 胆结石），胆结石数量（单发与多发），胆结石 直径和胆囊壁厚度使用超声检查; 2） 进行遗传分析以估计GBD的遗传力 表型，以检测与GBD易感性相关的初步证据 基因座，使用多点连锁分析来完善初始筛选， 并使用非参数方法检测连锁或关联。 将从720名个体中收集超声GBD表型数据 分布在32个家庭。最初的基因组筛选将基于 在涉及444名受试者的SAFADS家庭的子集上， 基于360多个标记的centiMorgan（cM）基因组图谱已经在 available.在检测到用于链接的潜在信号之后， 从全套SAFADS中获得分辨率为5 cM的基因图谱 家庭（720个人）将被用来精确定位 影响GBD表型的易感基因座。

DESCRIPTION: (Adapted from investigator's abstract) Gallbladder disease (GBD) is one of the major causes of morbidity and mortality in the United States. In populations such as the Mexican Americans, the prevalence of GBD is high, and it often clusters with diseases such as non-insulin dependent diabetes mellitus (NIDDM) and obesity. The etiology of GBD is unclear, but it is believed to be multifactorial in origin involving abnormalities of the hepatobiliary system such as supersaturation of bile with cholesterol, changes in cholesterol nucleation, and hypomotility of the gallbladder. Despite the epidemiological evidence for its association with risk factors such as age, sex (higher in women), obesity, native American ancestry, NIDDM, and cardiovascular disease risk factors, evidence for genetic determination of GBD is very limited. The purpose of this project is to conduct a genetic epidemiologic investigation involving molecular genetic data, GBD phenotypes, and statistical genetic techniques to examine the genetic basis for variation in GBD phenotypes in a set of 32 low-income Mexican American families that is currently under investigation in relation to the genetic determination of NIDDM (San Antonio Family Diabetes Study: SAFADS). The overall objectives of this study are to measure genetic effects on GBD phenotypes, and to identify and localized GBD susceptibility genes. The specific aims are 1) to define GBD phenotypes such as gallstone disease (presence of gallstones), gallstone number (solitary versus multiple), gallstone diameter, and gallbladder wall thickness using ultrasonography; 2) to perform genetic analysis in order to estimate heritabilities for GBD phenotypes, to detect initial evidence of linkage to GBD susceptibility loci, to refine the initial screening using multipoint linkage analysis, and to detect linkage or association using non-parametric methods. Ultrasound GBD phenotypic data will be collected from 720 individuals distributes across 32 families. The initial genome screening will be based on a subset of SAFADS families involving 444 subjects for whom the 10-15 centiMorgan (cM) genome map based on more than 360 markers is already available. After detecting potential signals for linkage, a high resolution 5 cM gene map to be obtained from a full set of SAFADS families(720 individuals) will be used to precisely localize susceptibility loci influencing GBD phenotypes.