Female Sexual Orientation GWAS

女性性取向 GWAS

• 批准号: 10435504
• 负责人: Eden R. Martin
• 金额: $ 61.1万
• 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/10435504
• 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 Women; 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. 项目概要/摘要 我们将对女性性取向的遗传学进行迄今为止规模最大、最全面的研究 （SO），一种具有重大科学和社会意义的遗传复杂性状，我们的研究将揭示根本性的问题。 我们建立了大型 GWAS 合作来实现我们的具体目标： 1. 对总共约 10,900 名同性恋、约 6,800 名双性恋、 我们提议对大约 359,700 名异性恋女性进行一项规模和范围前所未有的遗传研究。 我们将收集、协调和分析可用的全基因组基因分型数据。 为了对这些女性进行荟萃分析。 2. 对新收集的深度表型女性样本 (N=8,000) 进行 GWAS 与之前的样本 (N=1,949) 相比，总共 3,754 名同性恋、2,843 名双性恋和 3,352 名异性恋 这意味着从事基因研究的非异性恋女性数量增加了约 40%。 目标 1. 拟议的研究将填补几个空白，因为它将为 SO 和 比以前的研究具有相关特征，允许为未来的研究重新联系受试者，并快速共享 通过 NIH 数据共享机制，这个新样本集将发挥重要的统计作用。 增加总体样本量并更好地平衡非异性恋与异性恋女性的比例。 目标 1 和 2 的 GWAS 合并将包括 >387,000 名女性（加上 >347,000 名男性进行合并分析）。 3. 对目标 1 和 2 的数据进行多位点分析，深入了解功能 我们将研究基因座的影响并确定其他可能的基因目标。 分析以测试功能相关位点的累积效应，以及多基因评分分析以 描述女性 SO 的整体遗传结构。 4. 将相关表型/性状纳入分析中，以评估混杂因素和潜在遗传因素 我们将关注表型相关性并定义共享的遗传景观。 包括自杀、抑郁、焦虑、药物滥用、性别不安——来自文献和我们的研究 将进行一些初步数据分析：(a) 测试主要变异/基因，包括相关的变异/基因。 表型作为协变量来评估潜在的混杂因素，(b) 评估遗传力和遗传相关性 定量遗传效应并识别共享遗传成分，以及（c）进行多性状分析 利用相关表型中的信息。 通过绘制和表征导致性状变异的遗传变异，我们将提供重要的新发现 以及关于女性 SO 的遗传贡献的验证性见解，这是一个众所周知的研究不足的领域。 寻找相关且最终影响性状的遗传变异将为进一步研究打开大门 SO 发展的遗传和环境机制。