Development and Application of Phenome-wide Scan of Heritability (PheSH)

描述（由申请人提供）：了解疾病的遗传病因，无论是常见的还是罕见的，对于遗传学在“个性化医疗”中的应用至关重要。所有疾病都是环境和/或遗传因素共同作用的结果。由于遗传因素导致的疾病/性状的变异量被称为“遗传性”。如果没有通过遗传力测量得到的强有力的遗传成分的证据，进行遗传/基因组研究是困难的。遗传力可以在双胞胎或其他家庭结构中测量，但这是不可能的

DESCRIPTION (provided by applicant): Understanding the genetic etiology of diseases, both common and rare, is paramount to the application of genetics in "personalized medicine." All diseases are the result of a combination of environmental and/or genetic factors. The amount of variation in a disease/trait that is due to a genetic contribution is called "heritability." Conducing genetic/genomic studies is difficult without evidence of a strong genetic component by heritability measurements. Heritability can be measured in twins or other family structures, but is challenged by the resources required to collect the limited available families with appropriate phenotypic data. Moreover, even when these families are identified, heritability measurements are typically restricted to a single disease. The proposed research addresses these challenges by applying well-developed statistical methods in novel ways to simultaneously calculate heritability for many diseases using data available in the electronic medical record (EMR). The proposed project will test the hypothesis that thousands of clinical phenotypes, defined by patient medical records in families, can be used to measure heritability to direct further genetic/genomic studies. We call this novel bioinformatic method Phenome-wide Scan of Heritability (PheSH). The PheSH concept resulted from my work on Phenome-Wide Association Studies (PheWAS) conducted during my NLM-supported mentored training. Both PheWAS and PheSH are phenotype- independent approaches that allow for the genetic study of many clinical diseases or traits simultaneously. In the independent phase of my career, I plan to continue developing phenotype-independent techniques, including PheSH, to study the genetic etiology of human disease.