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Identification and Characterization of Genetic Risk Variants for Chronic Kidney Disease and Related Traits

慢性肾脏病及相关特征的遗传风险变异的鉴定和表征

基本信息

批准号：
159166183
负责人：
Professorin Dr. Anna Köttgen
金额：
--
依托单位：
Institut für Genetische Epidemiologie
依托单位国家：
德国
项目类别：
Independent Junior Research Groups
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/159166183?language=en
关键词：
Identification Characterization Genetic Risk Variants

项目摘要

Chronic kidney disease (CKD) constitutes a serious public health burden of increasing prevalence and incidence worldwide. It can progress to end-stage renal disease and increases the risk for cardiovascular morbidity and mortality substantially. Despite strong evidence for a genetic component, few genetic susceptibility loci for CKD have been identified to date. Understanding the underpinnings of genetic susceptibility to kidney disease can provide valuable insights into important physiological pathways and disease mechanisms. The objective of this proposal is therefore to expand on previous work to discover and characterize novel common and rare genetic susceptibility variants for kidney dysfunction and CKD. This objective will be addressed by first conducting genome-wide association studies of CKD and measures of kidney function in ~45,000 individuals of European ancestry within a large international consortium. Discovery will be followed by targeted resequencing of the most promising genes in fewer individuals, including the UMOD gene we identified previously. Follow-up genotyping of risk variants and their characterization will be conducted in population-based and CKD-specific study samples. Finally, because exact measurement of the phenotype is essential for comprehensive variant identification, a novel CKD biomarker, serum FGF-23, will be measured in 3,000 participants of a population-based study. Associations of FGF-23 levels with CKD and its complications will be studied, and genetic and non-genetic correlates of FGF-23 and other components of the FGF-23 pathway will be identified. Combined, the proposed studies will provide novel insights into the genetics of chronic kidney disease.

慢性肾脏病（CKD）在全球范围内的患病率和发病率不断增加，构成了严重的公共卫生负担。它可以进展为终末期肾病，并大大增加心血管发病率和死亡率的风险。尽管有强有力的证据表明存在遗传成分，但迄今为止，已确定的CKD遗传易感性位点很少。了解肾脏疾病遗传易感性的基础可以为重要的生理途径和疾病机制提供有价值的见解。因此，本提案的目的是扩展先前的工作，以发现和表征肾功能不全和CKD的新的常见和罕见遗传易感性变体。这一目标将通过首先在一个大型国际财团内的约45，000名欧洲血统个体中进行CKD的全基因组关联研究和肾功能测量来实现。在发现之后，将在更少的个体中对最有希望的基因进行靶向重测序，包括我们先前鉴定的UMOD基因。将在基于人群和CKD特异性研究样本中进行风险变体的随访基因分型及其表征。最后，由于表型的精确测量对于全面的变异识别至关重要，因此将在基于人群的研究的3，000名参与者中测量一种新的CKD生物标志物血清FGF-23。将研究FGF-23水平与CKD及其并发症的关联，并鉴定FGF-23和FGF-23途径的其他组分的遗传和非遗传相关性。结合起来，拟议的研究将为慢性肾脏疾病的遗传学提供新的见解。