Identifying Genes for Type 2 Diabetes: FUSION

描述(由申请人提供)： 2型糖尿病(T2 DM)是美国和世界各地发病率和死亡率的主要原因。虽然疾病的患病率各不相同，但据估计，20-74岁的美国人口中有6.6%患有T2 DM；芬兰也观察到了类似的比率。在美国，据估计，糖尿病占所有医疗保健支出的近七分之一。有大量证据表明，T2 DM的病因学中存在遗传成分。芬兰人群因其相对遗传同质性、出色的数据来源以及大力支持医学研究的人群，为研究T2 DM等复杂遗传疾病提供了理想的基础。芬兰-美国NIDDM遗传学调查(FUMP)研究的目标是确定易患T2 DM(以前的非胰岛素依赖型糖尿病或NIDDM)并导致T2 DM相关数量性状变异的遗传变异。作为融合的一部分，总共对4852名个体进行了抽样，其中包括855个通过受T2 DM影响的同胞对确定的家庭和231个独立的老年血糖正常对照及其家庭。对两组独立的T2 DM芬兰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绘制。在接下来的五年里，融合研究人员将对大约1700名融合家族成员进行采样和/或表型分析，对当前的融合样本进行有限的额外表型分析，获得大约600例T2 DM病例和大约800例对照的独立样本，精细绘制22、20和11号染色体区域的图谱，并试图确定相关的T2 DM易感变异。Fusion调查人员将通过继续参与国际T2 DM连锁分析联盟和其他新的和已建立的合作，继续并扩大与其他寻求绘制和克隆T2 DM变异的研究人员的合作。这项拟议的研究符合逻辑地建立在研究人员过去的工作基础上，并可能在接下来的项目期间识别一个或多个易患2型糖尿病的变种。这些努力将在很大程度上促进对T2 DM病因的了解，并为新的治疗和预防方法指明方向。在融合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.