Novel Statistical Approaches to Mental Health Phenotype Analysis in GWA Studies

描述（由申请人提供）：最近的科学和技术发展已经使全基因组关联研究成为现实。他们能否成功解开复杂疾病的遗传基础，将在很大程度上取决于能否有效应对此类研究所带来的统计挑战。将对数十万个SNP进行基因分型，并检查其与表型的潜在关联。全基因组关联研究必须将显著增加的SNP信息量转化为增加的统计能力。对于在全基因组关联研究中计算的统计检验的数量，用于处理多重检验问题的标准统计方法，例如错误发现率，过于保守，并且可能稀释任何真实的遗传信号。需要新的统计方法来处理这种规模的多个测试问题。我们将开发新的统计方法来解决全基因组关联研究中的这些主要障碍。我们新的统计方法将使研究人员能够研究复杂疾病的潜在遗传机制，如阿尔茨海默病和多动症。公共卫生相关性：阿尔茨海默病和ADHD是美国的主要公共卫生问题。我们的新统计方法将提供一套工具，研究人员和临床医生可以使用这些工具来识别影响这些疾病发展的因素（遗传或环境诱导）。反过来，更好地了解这些疾病的遗传机制可以更好地和更有效地照顾那些患有这些疾病或最有可能患上这些疾病的人。

DESCRIPTION (provided by applicant): Recent scientific and technological developments have made genome-wide association studies a reality. Their success in disentangling the genetic basis of complex diseases will depend largely on the efficient handling of the statistical challenges posed by such studies. Several hundred thousand SNPs will be genotyped and examined for the potential associations with phenotypes. Genome-wide association studies must translate the markedly increased amount of SNP-information into increased statistical power. For the number of statistical tests computed in a genome-wide association study, standard statistical methods for handling the multiple testing problem, such as false-discovery rate, are too conservative and are likely to dilute any true genetic signals. Novel statistical methodology is required to handle the multiple testing problems at this scale. We will develop novel statistical methodology to solve these major hurdles in genome-wide association studies. Our novel statistical methodology will enable researchers to examine the underlying genetic mechanism of complex diseases, such ad Alzheimer Disease and ADHD. PUBLIC HEALTH RELEVANCE: Alzheimer Disease and ADHD are major public health problems in the United States. Our novel statistical methodology will provide a set of tools, which researchers and clinicians can use to identify factors (inherited or environmentally-induced) that affect the development of these diseases. In turn, a better understanding of the genetic mechanisms of these conditions can result in better and more efficient care of those who suffer from - or are most at risk for the development of -these diseases.