Meta-Analysis of Male Sexual Orientation

 描述(由申请者提供)：这个项目将提供迄今为止关于男性性取向遗传学的最全面的研究。对性取向的病因和发展进行基础研究的主要理由包括，它具有很大的社会重要性和趣味性，这种研究将阐明大脑、精神和行为的性特征，从而向社会提供关于男性性取向背后目前未知的生物学方面的信息。众所周知，男性性取向是可遗传的，但本质上是多因素的，有多种遗传和环境因素导致其病因。遗传连锁研究已经发现了特定遗传位点(着丝粒周围8号染色体和Xq28号染色体)的强有力证据。关于性取向的全基因组关联研究才刚刚开始。有很大的需要结合研究来阐明这一重要生物学特征的遗传学。在这项建议中，我们计划对几个全基因组范围的连锁研究(GWLS)和GWAS进行荟萃分析，以最大限度地提高识别未来研究的遗传靶点的能力。我们的具体目标如下：1.通过对男性性取向的GWL进行Meta分析，确定最有希望的连锁区域：我们自己的GWL有409个GWP，加上其他合作GWL的155个GWL，总计564个Asps(占该领域Asps的91%)。2.使用我们的欧洲血统(EA)对701名同性恋者和1214名异性恋者的GWA，以及其他协作性GIA(目前总共5752名同性恋者和39,286名异性恋者，而且还在不断增加)进行关于男性性取向的现有GWA的荟萃分析。我们的结果将有助于更好地理解基因对男性性取向的贡献，并使未来旨在定位导致性状变异的遗传变异的方法成为可能，特别是Re 测序。发现连锁、关联或最终促成的遗传变异将打开进一步研究的大门，这些研究将为影响性取向的遗传和环境机制以及发育事件的研究提供信息。

 DESCRIPTION (provided by applicant): This project will provide the most comprehensive study to date on the genetics of male sexual orientation. The main justifications for basic research on the etiology and development of sexual orientation include that it carries much social importance and interest, and that such research will illuminate sexual characteristics of brain, mind and behavior, thus informing society about currently unknown biological aspects behind male sexual orientation. Male sexual orientation is known to be heritable, but is multifactorial in nature with multiple genetic and environmental factors contributing to its etiology. Genetic linkage studies have found strong evidence of specific genetic loci (pericentromeric chromosome 8 and chromosome Xq28). Genome-wide association studies (GWAS) for sexual orientation are only just beginning to surface. There is a great need to combine studies to elucidate the genetics of this important biological trait. In this proposal, we plan to conduct meta-analysis of several genome-wide linkage studies (GWLS) and GWAS to maximize the ability to identify genetic targets for future study. Our specific aims are as follows 1. Determine the most promising linkage regions by meta-analyzing GWLS for male sexual orientation: our own GWLS of 409 ASPs, plus other collaborative GWLS of 155 ASPs, totaling 564 ASPs (representing 91% of the field's ASPs). 2. Conduct a meta-analysis of available GWAS for male sexual orientation using our European ancestry (EA) GWAS of 701 homosexual and 1,214 heterosexual men, plus other collaborative GWAS, en masse currently totaling 5,752 homosexual and 39,286 heterosexual men, and growing. Our results will be instrumental to a better understanding of the genetic contributions to male sexual orientation and also enable future approaches aimed at locating genetic variants contributing to trait variation, especially re sequencing. Finding linkage, association, or eventually contributory genetic variants will open a gateway to additional research that will inform the study of genetic and environmental mechanisms and developmental events influencing sexual orientation.