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的重要遗传成分，这是正常人类性行为中最基本的变化之一。这份申请描述了由芝加哥大学的五名研究者、西北大学的一名研究者和芝加哥伊利诺伊大学的一名伦理学顾问组成的一项努力，他们被选中提供特殊的优势，以招募大量由同性恋兄弟组成的受影响的兄弟对（asp），并增加对这一特征的遗传贡献的理解。我们充分意识到，在没有足够规模的有益样本的情况下，这一领域的所有研究都面临着困难。在设计一种确定程序以消除获得更大样本的障碍方面，已经进行了相当多的思考。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。估计该性状的兄弟姐妹复发率（Isib）约为bh2比4。功率分析表明，1000个asp样本在检测复杂性状（如男性同性恋倾向）的易感位点方面具有相当大的能力：对于“暗示性”连锁，检测Isib大于1.25的位点的能力约为80% (p=0.00074)，对于“显著性”连锁，检测Isib大于1.3的位点的能力约为80% （p=0.000022）。

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.