Female Sexual Orientation GWAS

女性性取向 GWAS

• 批准号: 10197181
• 负责人: Eden R. Martin
• 金额: $ 61.53万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-20 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197181
• 关键词: Address; Alleles; Anxiety; Area; Basic Science; Behavior; Biocompatible Materials; Biological; Bisexual; Bisexuality; Childhood; Clinical; Collaborations; Complex; Data; Data Set; Detection; Development; Equilibrium; Family; Female; Festival; Future; Gender; Gene Targeting; General Population; Genetic; Genetic Markers; Genetic Research; Genetic study; Genotype; Goals; Heritability; Heterosexuality; Heterosexuals; Homosexuality; Homosexuals; Human; Individual; Knowledge; Life; Light; Literature; Maps; Mental Depression; Meta-Analysis; Methods; Minority; Molecular; Pathway Analysis; Pattern; Phenotype; Prevalence; Questionnaires; Recontacts; Research; Role; Sample Size; Sampling; Sampling Studies; Science; Sex Behavior; Sex Chromosomes; Sex Differentiation; Sex Orientation; Sexuality; Siblings; Societies; Suicide; Surface; Testing; Twin Multiple Birth; United States National Institutes of Health; Variant; Woman; experience; follow-up; gender dysphoria; genetic architecture; genetic variant; genome wide association study; genome-wide; genome-wide linkage; insight; interest; male; meetings; men; non-heterosexual; novel; posters; recruit; segregation; sex; sexual dimorphism; social; substance use; trait

7. PROJECT SUMMARY / ABSTRACT We will conduct the largest and most comprehensive study to date on the genetics of female sexual orientation (SO), a genetically complex trait of major scientific and social interest. Our research will uncover fundamental biological aspects of female SO. We have built a large GWAS collaboration to conduct our specific aims: 1. Conduct a meta-analysis of available GWAS datasets totaling ~10,900 homosexual, ~6,800 bisexual, and ~359,700 heterosexual women. We propose a study of unprecedented size and scope for the genetic study of female SO. We will assemble, harmonize, and analyze available genome-wide genotyping data in order to perform a meta-analysis on these women. 2. Conduct a GWAS on a deeply phenotyped, newly collected sample of women (N=8,000) combined with a previous sample (N=1,949), totaling 3,754 homosexual, 2,843 bisexual, and 3,352 heterosexual women. This represents a ~40% increase in the number of non-heterosexual women for genetic research over Aim 1. The proposed research will fill several gaps as it will provide more detailed phenotyping for SO and correlated traits than previous studies, allow for recontact of subjects for future studies, and be rapidly shared through an NIH data-sharing mechanism. This new sample set will serve an important statistical role by increasing the overall sample size and better balancing the ratio of nonheterosexual to heterosexual women. Aims 1 & 2 combined GWAS will be >387,000 women (plus >347,000 men for combined analyses). 3. Perform multi-locus analyses on the data from Aims 1 & 2, providing insight into functional implications of the loci and identifying additional possible genic targets. We will perform pathway analyses to test for the cumulative effect of functionally related loci, and polygenic score analysis to characterize the overall genetic architecture of female SO. 4. Incorporate correlated phenotypes/traits into analyses to assess confounding and potential genetic correlations and define the shared genetic landscape. We will focus on phenotypic correlations—, including suicidality, depression, anxiety, substance use, gender dysphoria—from the literature and our preliminary data. Several analyses will be conducted: (a) test top variants/genes including correlated phenotypes as covariates to assess potential confounding, (b) evaluate heritability and genetic correlations to quantify genetic effects and identify shared genetic components, and (c) conduct multi-trait analysis to leverage information in correlated phenotypes. By mapping and characterizing genetic variants contributing to trait variation, we will provide important novel and confirmatory insights regarding genetic contributions to female SO, a notoriously understudied area. Finding associated and eventually trait-influencing genetic variants will open a gateway to additional research on both genetic and environmental mechanisms of SO development.

7。项目摘要 /摘要 迄今为止，我们将对女性性取向的遗传学进行最大，最全面的研究 （因此），一个主要的科学和社会兴趣的一般复杂特征。我们的研究将发现基本 女性的生物学方面。我们已经建立了大型GWAS合作来实现我们的具体目标： 1。进行可用的GWAS数据集的荟萃分析，总计约10,900个同性恋，约6,800个双性恋， 和〜359,700名异性妇女。我们提出了一项关于遗传的前所未有的大小和范围的研究 女性研究。我们将组装，协调和分析可用的全基因组基因分型数据 为了对这些妇女进行荟萃分析。 2。在深层表型，新收集的女性样本（n = 8,000）上进行GWA 以前的样本（n = 1,949），总计3,754个同性恋，2,843个双性恋和3,352个异性恋 女性。这代表非异性恋妇女的遗传研究数量增加约40％ 目标1。拟议的研究将填补几个空白，因为它将为SO和SO和 相关性状比以前的研究相关，允许对未来研究的受试者进行重新连接，并迅速共享 通过NIH数据共享机制。这个新样本集将通过 增加总体样本量，并更好地平衡非焦点与异性恋女性的比率。 AIMS 1和2合并的GWA将> 387,000名女性（加上> 347,000名男性用于组合分析）。 3。对AIMS 1和2的数据进行多级别分析，提供有关功能的洞察力 基因座的含义并识别其他可能的基因靶标。我们将执行途径 分析以测试与功能相关的局部累积效应，以及多基因分析分析 表征女性的整体遗传结构。 4。将相关的表型/特征纳入分析，以评估混杂和潜在的遗传 相关并定义共享的遗传格局。我们将专注于表型相关性 - 包括自杀性，抑郁，焦虑，吸毒，性别烦躁不安 - 从文献和我们 初步数据。将进行几项分析：（a）测试顶级变体/基因，包括相关 表型作为协变量来评估潜在的混杂，（b）评估遗传力和遗传相关性 量化遗传效应并确定共有的遗传成分，（c）进行多特征分析 利用相关表型中的信息。 通过映射和表征有助于性状变化的遗传变异，我们将提供重要的新颖性 以及关于对女性遗传贡献的确认见解，这是一个众所周知的领域。 查找相关的，有时甚至是特质的遗传变异将为其他研究打开门户 关于SO发展的遗传和环境机制。