Genetics of water balance

水平衡的遗传学

基本信息

批准号：
8466312
负责人：
DAVID M COHEN
金额：
$ 34.06万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8466312
关键词：
Accounting Address Adverse effects Agreement Ancillary Study Antidepressive Agents Antipsychotic Agents Candidate Disease Gene Chronic Chronically Ill Clinical Code Cohort Studies Complication DNA Data Data Aggregation Data Set Databases Defect Development Disease Diuretics Duct (organ) structure Elderly Electrolytes Elements Equilibrium Ethnic Origin Exclusion Criteria Familial disease Family Framingham Heart Study Funding Gene Frequency Generations Genes Genetic Genetic Determinism Genetic Polymorphism Genomics Genotype Heart Heredity Heritability Human Human Genetics Hypernatremia Hyponatremia Hypothalamic structure In Vitro Intervention Medical Metabolism Minority Morbidity - disease rate Mutation National Health and Nutrition Examination Survey National Heart, Lung, and Blood Institute Parents Patients Pharmaceutical Preparations Phenotype Population Protein Isoforms Proteins Regulation Regulator Genes Risk Series Serum Severities Single Nucleotide Polymorphism Sodium United States National Institutes of Health Vasopressin Receptor Water aquaporin-2 base cohort density gene environment interaction genetic regulatory protein genome wide association study indexing interest men mortality non-genetic novel osteoporosis with pathological fracture outcome forecast public health relevance pyrosequencing sensor

项目摘要

DESCRIPTION (provided by applicant): Disorders of water metabolism are common among the elderly, the acutely and chronically ill, and among patients taking certain medications. Abnormal water balance is detected clinically by an increase or decrease in the serum sodium concentration (hyper- and hyponatremia, respectively). Hyponatremia is the most common of the electrolyte abnormalities and even a modest reduction in serum sodium concentration (i.e., water excess) is associated with substantial morbidity and mortality. Rare mutations in water-regulatory genes cause familial abnormalities of water balance; however, these account for only a small minority of cases of hyponatremia. Our preliminary data strongly support the heritability of systemic water balance; in addition, we have identified a non-synonymous polymorphism in a water-regulatory gene that is associated with hyponatremia in several human populations. No prior studies have addressed the genetics of water balance on a population-wide basis and there is at present no way to predict who is at greatest risk from medications or disease states statistically associated with the development of hyponatremia. The over-arching objective of this proposal is to define the genetics of systemic water balance on a population-wide basis using data derived from prior large-scale NHLBI-sponsored (and other NIH-sponsored) cohort and family-based studies. In Aim I, we will quantify the heritability of water balance in additional human populations using data from family-based components of large NHLBI-funded cohort studies. In Aim II, we will identify human genetic polymorphisms associated with aberrant water balance via a candidate gene approach. Banked genomic DNA previously obtained in the course of large NHLBI-funded cohort studies will be used. In Aim III, genome-wide association studies will be performed to identify in an unbiased fashion genetic polymorphisms associated with aberrant systemic water balance in large cohorts. For this Aim, we will use high-density genotyping data generated as part of ongoing analysis in several NHLBI-funded cohort studies. Through this combination of approaches made possible by NHLBI-supported data generation, we hope to elucidate the human genetic basis for systemic water balance and identify polymorphisms associated with hypo- and hypernatremia.

描述（由申请人提供）：水代谢的疾病在老年人，急性和长期疾病以及服用某些药物的患者中很常见。通过血清钠浓度的增加或降低（分别高血和低钠血症），在临床上检测到水平衡异常。低钠血症是最常见的电解质异常，甚至血清钠浓度（即水过量）的适度降低与大量发病率和死亡率有关。水调节基因的罕见突变会导致家族性水平的家族异常。但是，这些仅解释了少数低钠血症病例。我们的初步数据强烈支持全身水平衡的遗传力；此外，我们已经确定了在水调节基因中与低钠血症相关的非同义性多态性。先前的研究尚无人口范围的水平遗传学，目前无法预测谁在药物或疾病状态统计学上与低钠血症的发展相关的最大风险。该提案的整个目标是使用从先前的大规模NHLBI赞助的（和其他NIH赞助的）同类研究和基于家庭的研究中得出的数据来定义全身水平衡的遗传学。在AIM I中，我们将使用大型NHLBI资助的队列研究的基于家庭组成部分的数据来量化其他人群中水平的遗传力。在AIM II中，我们将通过候选基因方法确定与异常水平相关的人类遗传多态性。将在大型NHLBI资助的队列研究过程中先前获得的库存基因组DNA。在AIM III中，将进行全基因组的关联研究，以识别与大型同类群体中异常全身水平衡相关的无偏见遗传多态性。为此，我们将使用几项NHLBI资助的队列研究中正在进行分析的一部分生成的高密度基因分型数据。通过NHLBI支持的数据生成的这种方法的结合，我们希望阐明全身水平平衡的人类遗传基础，并鉴定与低钠和高钠血症相关的多态性。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evaluating hyponatremia.

评估低钠血症。

DOI：
10.1001/jama.2014.13967
发表时间：
2015
期刊：
JAMA
影响因子：
0
作者：
Cohen,DavidM;Ellison,DavidH
通讯作者：
Ellison,DavidH

Individuality of the plasma sodium concentration.

血浆钠浓度的个体性。

DOI：
10.1152/ajprenal.00585.2013
发表时间：
2014
期刊：
American journal of physiology. Renal physiology
影响因子：
0
作者：
Zhang,Zheng;Duckart,Jonathan;Slatore,ChristopherG;Fu,Yi;Petrik,AmandaF;Thorp,MicahL;Cohen,DavidM
通讯作者：
Cohen,DavidM

A reversible cause of 'end-stage renal disease': discrepant findings in serial duplex ultrasonograms in a suspected occlusion of a renal arterial bypass graft.