Familial Female Sexual Orientation Phenotypes

说明(由首席调查员提供)：本申请包括一个网站，辅以三名顾问，申请R21机制下的“家族性取向表型”。长期目标是更好地了解基因对性取向特征的影响，性取向是人类行为中最重要的变量之一，在心理学和生物学领域都是如此。由于性是人类生活中必不可少的一部分，了解包括性取向在内的人类正常的性发育是很重要的。女性的性取向在某些方面与男性有很大的不同，与男性的性取向相比，女性的性取向研究不足。这既包括前分子方法(例如，家庭和双胞胎研究)，也包括特别是分子方法(即，基因图谱)。这一R21将通过一项家庭研究来解决这一知识差距，该研究旨在探索女性性取向与相关表型(流动性、性别不一致和利手)之间的关系。这将指导分子方法的进一步工作，特别是将成为随后R01应用的焦点的全基因组关联研究(GWAS)。目前的R21研究的具体目标是：(A)确定最具家族性的女性性取向表型。在一项家庭研究(N=2,000)中，将评估以下各项：女性性取向、流动性(即，性取向方面的波动)、性别不一致、先证者(指标家庭成员)的利手与先证者女性亲属的性取向；(B)通过比较先证者的流动性比率和先证者的女性亲属的流动性(通过先证者报告，即家族史方法)，对女性的性流动性进行第一次家庭研究；(C)收集从唾液和唾液中提取的DNA样本，作为R01申请基于人群的病例对照GWAS的试点数据/生物材料。招募将包括1000名同性恋骄傲节的先驱和1000名普通社区节日的先驱，产生约1000名女同性恋者或双性恋者和约1000名异性恋女性先驱。这些先驱者完成关于他们的性取向、流动性、性别不一致和利手的问卷调查。该遗嘱还将提供有关其女性一级和二级亲属的性取向和流动性的信息(预计每个先证者约有9名此类亲属)。在约500名先证者的子集上，还将通过在线相同的匿名问卷直接从他们的亲属那里收集问卷数据，以验证通过家族史方法获得的信息。初步分析表明，在所建议的样本量下，这些目标可以通过较高的统计能力来实现。 公共卫生相关性：性取向是人类行为中最重要的变化之一，对其发展的贡献在很大程度上是未知的，尽管与女性相比，男性的研究更广泛。由于性是人类生活的重要组成部分--对个人和社会而言--理解人类正常的性发育，包括性取向，是很重要的。此外，有关性行为的事实信息可以帮助防止扭曲和敌意的观点。

DESCRIPTION (provided by principal investigator): This application consists of one site, complemented by three consultants, for the application "Familial Female Sexual Orientation Phenotypes" under the R21 mechanism. The long-term goal is to better understand genetic contributions to the trait of sexual orientation, one of the most important variations in human behavior, both in the realms of psychology and biology. Because sexuality is an essential part of human life, it is important to understand normal human sexual development, including sexual orientation. Female sexual orientation is strikingly different in some aspects, and understudied compared to male sexual orientation. This includes both pre-molecular approaches (e.g., family and twin studies) and especially in molecular approaches (i.e., genetic mapping). This R21 will address this knowledge gap by means of a family study to explore the relationship between female sexual orientation and associated phenotypes (fluidity, gender nonconformity, and handedness). This will guide further work with molecular approaches, especially a genome-wide association study (GWAS) that will be the focus of an ensuing R01 application. The current R21 study specific aims are: (A) to determine the most familial female sexual orientation phenotype. In a family study (N = 2,000) the following will be assessed: female sexual orientation, fluidity (i.e., fluctuation in aspects of sexual orientation), gender nonconformity, and handedness of probands (index family members) versus sexual orientation in the probands' female relatives; (B) to conduct the first family study of female sexual fluidity by comparing rates of fluidity in probands with fluidity in the probands' female relatives (by proband report, i.e., the family history method); and (C) to collect proband saliva-derived DNA samples as pilot data/biomaterials for an R01 application for a population-based case-control GWAS. Recruitment will include both 1,000 probands from Gay Pride festivals and 1,000 probands from general community festivals, resulting in ~1,000 lesbian or bisexual and ~1,000 heterosexual female probands. These probands complete questionnaires about their sexual orientation, fluidity, gender nonconformity, and handedness. The will also provide information on sexual orientation and fluidity of their female first- and second-degree relatives (expecting about 9 such relatives per proband). On a subset of ~500 probands, questionnaire data will also be collected directly from their relatives by means of the same anonymous questionnaire online to validate the information obtained by the family history method. Preliminary analyses suggest that for the proposed sample size, these aims can be achieved with high statistical power. PUBLIC HEALTH RELEVANCE: Contributions to the development of sexual orientation, one the most important variations in human behavior, are largely unknown, though more extensively studied in males compared to females. Because sexuality is an essential part of human life - for individuals and society - it is important to understand normal human sexual development, including sexual orientation. Furthermore, factual information about sexuality can help prevent distorted and hostile views.