Familial Female Sexual Orientation Phenotypes

描述（由首席研究员提供）：本申请由一个网站组成，由三名顾问补充，用于R21机制下的“家族性女性性取向表型”申请。长期目标是更好地理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化之一，在心理学和生物学领域都是如此。因为性是人类生活的重要组成部分，所以了解人类正常的性发展，包括性取向，是很重要的。女性的性取向与男性的性取向相比在某些方面有着显著的不同，而且还没有得到充分的研究。这包括前分子方法（例如，家庭和双胞胎研究），特别是分子方法（例如，遗传作图）。本R21将通过一项家庭研究来探讨女性性取向与相关表型（流动性、性别不一致性和利手性）之间的关系，从而解决这一知识差距。这将指导分子方法的进一步工作，特别是全基因组关联研究（GWAS），这将是随后R01应用的重点。目前R21研究的具体目的是：(A)确定最具家族性的女性性取向表型。在一项家庭研究中（N = 2,000）将评估以下内容：先证者（指数家庭成员）的女性性取向、流动性（即性取向方面的波动）、性别不一致和利手性与先证者女性亲属的性取向；(B)通过比较先证者与其女性亲属的性流动性比率，进行首次女性性流动性家庭研究（通过先证者报告，即家族史方法）；(C)收集先证者唾液来源的DNA样本，作为R01应用于基于人群的病例对照GWAS的试点数据/生物材料。招募将包括来自同性恋骄傲节的1000名先证者和来自一般社区节日的1000名先证者，结果是约1000名女同性恋或双性恋者和约1000名异性恋女性先证者。这些先证者完成关于他们的性取向、流动性、性别不一致性和惯用手的问卷调查。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个此类亲属）。在约500个先证者的子集中，通过同样的匿名在线问卷直接从其亲属中收集问卷数据，以验证家族史方法获得的信息。初步分析表明，对于建议的样本量，这些目标可以实现高统计功率。

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.