GENETICS OF GALLBLADDER DISEASE IN MEXICAN AMERICANS

描述：(改编自调查者摘要)胆囊病 (GBD)是美国发病率和死亡率的主要原因之一。 各州。在像墨西哥裔美国人这样的人群中， 血糖浓度高，常与非胰岛素等疾病聚集 依赖型糖尿病(NIDDM)和肥胖。GBD的病因是 不清楚，但据信它的起源是多因素的，涉及 肝胆系统异常，如胆汁过饱和 对于胆固醇，胆固醇成核的变化，以及运动功能低下 胆囊炎。尽管有流行病学证据表明它与 风险因素，如年龄、性别(女性比例较高)、肥胖、土生土长 美国血统、NIDDM和心血管疾病风险因素， 关于GBD基因决定的证据非常有限。 该项目的目的是进行遗传流行病学研究。 调查涉及分子遗传学数据、GBD表型和 检验变异遗传基础的统计遗传学技术 在32个低收入墨西哥裔美国家庭中的GBD表型 目前正在接受与基因决定有关的调查 NIDDM(圣安东尼奥家庭糖尿病研究：SAFADS)。整体而言 本研究的目的是测量遗传效应对GBD表型的影响， 并对GBD易感基因进行鉴定和定位。具体目标 1)确定GBD的表型，如胆石症(存在 胆结石)、胆结石数量(单发还是多发)、 超声检查胆囊壁厚度和直径；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，为了利用多点连锁分析改进初始筛查， 并使用非参数方法检测链接或关联。 超声的GBD表型数据将从720个个体中收集 分布在32个家庭。最初的基因组筛选将基于 关于涉及444名受试者的SAFADS家庭子集，其中10-15 基于360多个标记的centiMorgan(Cm)基因组图已经 可用。在检测到用于链接的潜在信号后，高 从全套SAFADS中获得分辨率5 cM的基因图谱 家庭(720个人)将用于精确本地化 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.