GENES, ADOLESCENT ADJUSTMENT, AND FAMILY PROCESSES

近年来，在定量和分子遗传学方面取得了重大进展。在数量遗传学中已经得出的压倒性的结论是，遗传因素对大多数调整措施都很重要。更令人惊讶的是，遗传因素对家庭进程的测量也有实质性的影响。基因分型、候选基因的鉴定以及分子遗传学中关联策略的使用，使得研究基因与连续分布特征（如调节）之间的关联成为可能。这个为期三年的项目旨在结合这些进展，利用候选基因关联来检查青少年的适应能力。此外，本研究将扩展这一策略，以探索家庭过程在调节和调解青春期基因表达中的作用。遗传物质（脸颊刮痕）将从参加青少年发展非共享环境项目（NEAD）的720个家庭样本中的两个兄弟姐妹（时间1为10至18岁）和父母双方收集。NEAD是nimh赞助的项目（MH-43373和MH-48825），评估两次，间隔三年，重点了解青少年适应以及遗传因素和家庭过程在形成适应中的作用。这是唯一的定量遗传研究，密集地测量了家庭过程，包括观察性评估。从该样本中收集遗传物质将能够检查(1)候选基因与青少年适应的关联，(2)候选基因与调节的纵向关联，(3)作为基因表达调节因子的家庭过程（基因型-环境相互作用），以及(4)作为基因表达介质的家庭过程（基因型-环境相关性）。包括兄弟姐妹和父母将允许使用不受人口分层影响的对照组策略。例如，将对兄弟姐妹中的一个成员进行候选基因关联，然后将另一个兄弟姐妹用于复制。由于NEAD是一个定量的遗传样本，因此可以计算遗传力以确定与候选基因最有可能关联的可能性（即，具有最大遗传力的测量是最佳起点）。此外，NEAD通过使用多测量、多药物评估，对表型进行了仔细的测量。这一建议利用了数量遗传学的最新进展和分子遗传学的最新进展，对于揭示基因如何影响发育的问题具有很大的潜力。

In recent years there have been major advances in quantitative and molecular genetics. The overwhelming conclusion that has been reached in quantitative genetics is that genetic factors are important for most measures of adjustment. More surprisingly, genetic factors also have substantial influence on measures of family processes. Advances in genotyping, the identification of candidate genes, and the use of association strategies in molecular genetics have allowed for the investigation of associations between genes and continuously distributed characteristics, like adjustment. The proposed three-year project seeks to combine these advances to use candidate gene association to examine adolescent adjustment. In addition, this research will extend this strategy to explore the role of family processes in both moderating and mediating gene expression during adolescence. Genetic material (cheek scrapings) will be collected from two siblings (ages 10 to 18 at time 1) and both parents from the sample of 720 families who participated in the Nonshared Environment in Adolescent Development Project (NEAD). NEAD is a NIMH-sponsored project (MH-43373 and MH-48825), assessed twice, three years apart, focused on understanding adolescent adjustment and the role of genetic factors and family processes in shaping adjustment. This is the only quantitative genetic study that has intensively measured family processes, including observational assessments. The collection of genetic material from this sample will enable the examination of (1) candidate gene associations with adolescent adjustment, (2) longitudinal associations of candidate genes and adjustment, (3) family processes as moderators of gene expression (genotype-environment interactions), and (4) family processes as mediators of gene expression (genotype-environment correlations). The inclusion of siblings and parents will allow the use of control group strategies that are not affected by population stratification. For example, candidate gene associations will be conducted for one member of the sibling pair and the other sibling is then used for replication. Because the NEAD is a quantitative genetic sample, heritabilities can be computed to identify the most likely possibilities for association with candidate genes (i.e., those measures with the largest heritabilities are the best starting points). In addition, NEAD employed careful measurement of phenotypes, through the use of multi-measure, multi-agent assessment. This proposal, using the most recent advances in quantitative genetics and the most recent advances in molecular genetics has great potential for informing the question of how genes influence development.