Implementing Appropriate Multivariate Methods for Higher Quality Results from Gen

描述（由申请人提供）：目前，明显缺乏精通（生物）统计的研究人员和专门为药物滥用遗传学研究设计的适当统计工具。最近的NIDA执行摘要强调了这一点，该摘要对药物滥用人群的全基因组和更普遍的遗传学研究的解释表示谨慎（国家药物滥用研究所[NIDA]， 2010）。该报告强烈建议NIDA将其资源用于“增加对生物统计学、统计遗传学和相关生物信息学学科培训的支持——这些学科是人员短缺已经成为制约因素的关键支持学科。”（NIDA, 2010，第iv页）。通过这一建议，我的目标是通过接受和提供适当的培训来减少1)“人员短缺”，以及2)GWAS在药物滥用研究中缺乏适当的工具。最近，《科学》（Science）杂志（Pennisi, 2007）发表了基因组全关联研究（Genome Association Studies， GWAS），并将其誉为一项“突破”。例如，最近的一项搜索结果在1008个（www.gwascentral.org）到26100多个（谷歌Scholar） GWAS结果之间。GWAS有潜力揭示复杂疾病的遗传贡献，并阐明涉及其病因的生物系统，但只有有效的方法方法。但是，尽管有如此广泛的应用，GWAS尚未产生任何“突破性”的结果，特别是在药物滥用方面（Hutchison, 2010）。此外，gwa数量的增长——尤其是在酒精和药物成瘾研究中（Hutchinson, 2010; Loth, Carvalho & Schumann, 2011）——并没有与能够充分利用这些复杂数据集的严格统计方法或工具的增长同步。在药物滥用GWAS方面缺乏突破可能是由于在适当的统计技术方面缺乏突破。统计工具的发展可以极大地促进在药物滥用和依赖的遗传学方面的新发现，例如新的遗传标记、环境影响和内表型。在这个建议中，我有两个主要的科学目标：1)开发并提供适当的工具（免费）用于药物滥用中的GWAS， 2)应用适当的工具来阐明冲动行为和药物滥用（大麻，尼古丁和暴饮暴食人群）的遗传和环境影响。目前的初步结果显示：1)遗传标记的复制和2)药物滥用的新遗传标记。初步结果显示神经肽Y （NPY）标记与暴饮暴食和多物质使用者的关系比其他任何组都要密切。此外，我已经确定了几个可能与BDNF和MAOA基因相关的保护性标记。

DESCRIPTION (provided by applicant): Currently, there is a distinct shortage of (bio) statistically proficient researchers and appropriate statistical tools designed by, and especially for, research in the genetics of substance abuse. This is underscored by the recent NIDA executive summary that expressed caution on the interpretation of genome-wide-and more generally, genetics-studies for substance abuse populations (National Institute on Drug Abuse [NIDA], 2010). The report strongly recommended that NIDA place its resources towards an "increase [in] support for training in biostatistics, statistical genetics, and related bioinformatcs disciplines-key support disciplines in which personnel shortages are already a constraint." (NIDA, 2010, p. iv). With this proposal, I aim to decrease both the 1) "personnel shortage" by receiving and providing appropriate training and 2) lack of appropriate tools for GWAS in substance abuse research. Recently appeared and hailed as a "breakthrough" by the journal Science (Pennisi, 2007) Genome Wide Association Studies (GWAS) are already used in many fields. For example, a recent search resulted in number of studies between 1,008 (www.gwascentral.org) to over 26,100 (Google Scholar) GWAS results. GWAS have the potential to shed light on the genetic contributions of complex disorders and elucidate the biological systems involved in their etiology, but only with valid methodological approaches. But despite such a range of applications, GWAS have yet to yield any "breakthrough" results, especially in substance abuse (Hutchison, 2010). Additionally, the growth in the number of GWAS-especially in alcohol and drug addiction research (Hutchinson, 2010; Loth, Carvalho & Schumann, 2011)-is not paralleled by a growth of rigorous statistical methods or tools that could fully exploit these complex data sets. This lack of breakthroughs in GWAS for substance abuse may be due to the lack of breakthroughs in appropriate statistical techniques. Statistical tool development could greatly facilitate new discoveries in the genetics of substance abuse and dependence, such as novel genetic markers, environmental influences and endophenotypes. In this proposal I have two primary scientific aims: 1) develop and make available appropriate tools (freely) for GWAS in substance abuse and 2) apply appropriate tools in order to elucidate the genetic and environmental influences of impulsive behaviors and substance abuse (in marijuana, nicotine and binge eating populations). Current preliminary results show both 1) replication of genetic markers and 2) novel genetic markers for substance abuse. Preliminary results show neuropeptide Y (NPY) markers are more associated to binge eating and polysubstance users than any other group. Additionally, I have identified several possibly protective markers related to the BDNF and MAOA genes.