Identifying Genes for Type 2 Diabetes:FUSION

描述（由申请人提供）： 2型糖尿病（T2DM）是美国和世界各地发病率和死亡率的主要原因。虽然患病率各不相同，但据估计，美国20 - 74岁人群中有6.6%患有T2DM;在芬兰也观察到类似的患病率。据估计，在美国，糖尿病占所有医疗保健支出的近1/7。有大量证据表明T2DM的病因学中存在遗传成分。芬兰人口提供了一个理想的基础，复杂的遗传疾病，如2型糖尿病的研究，由于其相对的遗传同质性，良好的数据来源，并大力支持医学研究的人口。芬兰-美国NIDDM遗传学调查（FUSION）研究的目的是确定易患T2DM（以前称为非胰岛素依赖型糖尿病或NIDDM）并导致T2DM相关数量性状变异的遗传变异。作为FUSION的一部分，共对4852名个体进行了采样，其中包括通过T2DM影响的兄弟姐妹对确定的855个家庭和231名独立的血糖正常的老年人及其家庭。对芬兰两组独立的2型糖尿病家庭的基因组扫描已经完成，并开始对几个染色体区域进行精细定位。在接下来的五年里，FUSION研究人员将对FUSION家族的大约1700个额外成员进行采样和/或表型分析，对当前FUSION样本进行有限的额外表型分析，获得约600例T2DM病例和约800例对照的独立样本，对22、20和11号染色体的区域进行精细定位，并寻求识别相关的T2DM易感变异体。FUSION研究人员将继续并扩大与其他研究人员的合作，通过继续参与国际T2DM连锁分析联盟和其他新的和已建立的合作，寻求映射和克隆T2DM变异。拟议的研究在逻辑上建立在研究人员过去的工作，并可能导致在未来的项目期间识别一个或多个T2DM易感变异。这些努力将有助于提高对T2DM病因学的认识，并为新的治疗和预防方法指明方向。在FUSION中开发的方法和吸取的经验教训也将有助于其他复杂遗传疾病的研究。

DESCRIPTION (provided by applicant): Type 2 diabetes (T2DM) is a major cause of morbidity and mortality in the USA and around the world. While disease prevalence varies, it has been estimated that 6.6 percent of the US population aged 20-74 years suffers from T2DM; similar rate has been observed in Finland. In the US, it has been estimated that diabetes is responsible for nearly 1/7 of all health care expenditures. There is substantial evidence of a genetic component in the etiology of T2DM. The Finnish population provides an ideal basis for studies of complex genetic diseases such as T2DM due to its relative genetic homogeneity, excellent data sources, and a population strongly supportive of medical research. The goal of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genetic variants that predispose to T2DM (formerly non-insulin-dependent diabetes mellitus or NIDDM) and are responsible for variability in T2DM-related quantitative traits. As part of FUSION, a total of 4852 individuals have been sampled, including 855 families ascertained through T2DM-affected sibling pairs and 231 independent elderly normoglycemic controls and their families. Genome scans on two independent sets of T2DM Finnish families have been completed, and fine mapping of several chromosomal regions has begun. In the next five years, FUSION investigators will sample and/or phenotype approximately 1700 additional members of the FUSION families, carry out limited additional phenotyping of current FUSION samples, obtain independent samples of about 600 T2DM cases and about 800 controls, fine map regions of chromosomes 22, 20, and 11, and seek to identify the relevant T2DM-predisposing variants. FUSION investigators will continue and expand collaborations with other investigators seeking to map and clone variants for T2DM, through continued involvement in the International T2DM Linkage Analysis Consortium and other new and established collaborations. The proposed research builds logically on the investigators' past work, and will likely result in identification of one or more T2DM-predisposing variants during the coming project period. These efforts should contribute in a significant way to improved understanding of the etiology of T2DM, and point the way to novel methods of treatment and prevention. Methods developed and lessons learned in FUSION will also be useful in the study of other complex genetic diseases.