Department of Child and Adolescent Psychiatry, LVR-Klinikum Essen, University of Duisburg-Essen, Virchowstrasse 174, Essen, Germany.
Eur Child Adolesc Psychiatry. 2010 Mar;19(3):259-79. doi: 10.1007/s00787-010-0091-y. Epub 2010 Feb 6.
The current status of child and adolescent psychiatric genetics appears promising in light of the initiation of genome-wide association studies (GWAS) for diverse polygenic disorders and the molecular elucidation of monogenic Rett syndrome, for which recent functional studies provide hope for pharmacological treatment strategies. Within the last 50 years, tremendous progress has been made in linking genetic variation to behavioral phenotypes and psychiatric disorders. We summarize the major findings of the Human Genome Project and dwell on largely unsuccessful candidate gene and linkage studies. GWAS for the first time offer the possibility to detect single nucleotide polymorphisms and copy number variants without a priori hypotheses as to their molecular etiology. At the same time it is becoming increasingly clear that very large sample sizes are required in order to enable genome wide significant findings, thus necessitating further large-scaled ascertainment schemes for the successful elucidation of the molecular genetics of childhood and adolescent psychiatric disorders. We conclude by reflecting on different scenarios for future research into the molecular basis of early onset psychiatric disorders. This review represents the introductory article of this special issue of the European Child and Adolescent Psychiatry.
当前儿童和青少年精神病遗传学的现状看起来很有希望，因为已经开始对多种多基因疾病进行全基因组关联研究 (GWAS)，并且阐明了单基因雷特综合征的分子机制，最近的功能研究为药物治疗策略提供了希望。在过去的 50 年中，在将遗传变异与行为表型和精神障碍联系起来方面取得了巨大进展。我们总结了人类基因组计划的主要发现，并详细讨论了候选基因和连锁研究的主要发现。GWAS 首次提供了检测单核苷酸多态性和拷贝数变异的可能性，而无需对其分子病因学进行先验假设。同时，越来越明显的是，为了能够进行全基因组显著发现，需要非常大的样本量，因此需要进一步进行大规模的确定方案，以便成功阐明儿童和青少年精神障碍的分子遗传学。最后，我们对未来研究早期发病精神障碍的分子基础的不同方案进行了反思。这篇综述代表了本期《欧洲儿童和青少年精神病学》特刊的介绍性文章。
