Molecular Genetic Study of Sexual Orientation

描述(由申请人提供)：家庭和双胞胎研究支持男性同性恋特征中的重要遗传成分，这是正常人类性行为中最基本的变异之一。本申请描述了由芝加哥大学的五名研究人员、西北大学的一名研究人员和伊利诺伊大学芝加哥分校的一名伦理学家顾问组成的努力，他们被选中提供特殊优势，以招募大量由同性恋兄弟组成的受影响的同胞对(ASP)，并增加对这一特征的基因贡献的理解。我们充分认识到，这一领域的所有研究在没有足够大的惠益样本的情况下研究这一领域都面临困难。为了设计一种确定程序，消除了获得更大样本的障碍，已经进行了大量的思考。我们设计了我们的研究，以便在三年内实现1,000个ASP的总样本。对该性状的兄弟姐妹复发率(ISIB)的估计约为bh2至4。功率分析表明，1,000个ASP样本将具有相当大的能力来检测复杂性状的易感基因座，如男性同性恋取向：大约80%的能力检测ISIB大于1.25时的“暗示”连锁(p=0.00074)，约80%的能力检测ISIB大于1.3时的“显著”连锁(p=0.000022)。 所有调查人员在现代家庭研究方法和确定男性同性恋取向表型的程序(Kinsey评分5-6)方面都有经验。所有网站都有合作研究的经验，其中一个网站收集了迄今为止最大规模的男性同性恋取向连锁研究的样本，另一个网站在男性同性恋取向的家庭和双胞胎研究过程中收集了类似的样本。我们由经验丰富的研究人员在全区和全国范围内进行的大规模招募工作，将确保通过上述机会主义确定，我们可以在3年内招募1000对同性恋兄弟。该项目的第4年和第5年致力于完成10厘米的基因组扫描、精细绘图、关联分析，以及对兄弟般的出生顺序效应和儿童性别不一致的数量性状的二次分析。

DESCRIPTION (provided by applicant): Family and twin studies support a significant genetic component in the trait of male homosexuality, one of the most fundamental variations in normal human sexuality. This application describes an effort composed of five investigators at the University of Chicago, one investigator at Northwestern University, and one ethicist consultant at the University of Illinois at Chicago, whom have been selected to provide special strengths for recruiting a large number of affected sib pairs (ASPs) comprised of homosexual brothers, and increasing the understanding of the genetic contributions to this trait. We are fully aware of the difficulties that all studies in this field have faced in studying this area without the benefit samples of adequate size. Considerable thought has gone into designing an ascertainment procedure that eliminates obstacles to achieving a larger sample. We have designed our study so that a total sample of 1,000 ASPs can be achieved within three years. An estimate of the sibling recurrence ratio (Isib) for the trait is approximately bh2 to 4. Power analyses demonstrate that a sample of 1,000 ASPs will have substantial power to detect predisposing loci for a complex trait such as male homosexual orientation: approximately 80% power to detect loci Isib greater than 1.25 for "suggestive" linkage (p=0.00074), and approximately 80% power to detect loci Isib greater than 1.3 for "significant" linkage (p=0.000022). All of the investigators are experienced in modern family study methods and in procedures for establishing the phenotype of male homosexual orientation (Kinsey score of 5-6). All are experienced in collaborative research studies, with one site having collected samples for the largest linkage study of male homosexual orientation to date, and the other site having collected similar samples in the course of family and twin studies of male homosexual orientation. Our large region-wide and national recruitment efforts by experienced researchers will ensure that we can recruit 1,000 pairs of homosexual brothers within 3 years through the above opportunistic ascertainment. Years 4 and 5 of the project are dedicated to completing a 10cM genome scan, fine-mapping, association analyses, and the secondary analyses for the fraternal birth order effect and the quantitative trait of childhood gender nonconformity.