Simón-Sánchez Javier, Singleton Andrew
Molecular Genetics Section, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Lancet Neurol. 2008 Nov;7(11):1067-72. doi: 10.1016/S1474-4422(08)70241-2.
During the past decade, the genetic causes of monogenic forms of disease have been successfully defined; this work has helped the progression of basic scientific investigation into many disorders, and has helped to characterise several molecular biological processes. An important goal of genetic research is to extend this work and define genetic risk factor loci for complex disorders. The aim is for these data not only to offer further basic understanding of the disease process, but also to provide the opportunity to obtain genetic risk assessments that could be generalised to the public.
The development of resources such as the Human Genome Project and the International Human Haplotype Map Project, coupled with technological advances in ultra-high-throughput genotyping, have provided the basis for genome-wide association studies (GWAS). This approach has been successful for several complex disorders in a short time. Although GWAS are still a new method, these studies have been used for a small number of neurological disorders and, despite varied results for these conditions, GWAS can usefully show the power and limitations of this approach. WHERE NEXT?: GWAS have the potential to show and emphasise common genetic variability associated with disease. However, a challenge of this approach is that large sample series and considerable resources are required. One important consideration will be the interpretation of the results of GWAS in a clinically meaningful way and to discern the implications for all therapy areas, including neurological disorders; this challenge will require specialised skills and resources from both the medical and the scientific communities.
在过去十年中，单基因疾病形式的遗传病因已得到成功确定；这项工作推动了对许多疾病的基础科学研究进展，并有助于描述若干分子生物学过程。遗传研究的一个重要目标是扩展这项工作，并确定复杂疾病的遗传风险因素位点。目的是使这些数据不仅能提供对疾病过程的进一步基础理解，还能提供获得可推广至公众的遗传风险评估的机会。
人类基因组计划和国际人类单倍型图谱计划等资源的开发，以及超高通量基因分型技术的进步，为全基因组关联研究（GWAS）提供了基础。这种方法在短时间内已成功应用于多种复杂疾病。尽管GWAS仍是一种新方法，但这些研究已用于少数神经系统疾病，尽管这些疾病的结果各不相同，但GWAS能有效地显示这种方法的优势和局限性。
GWAS有潜力展示并强调与疾病相关的常见遗传变异性。然而，这种方法面临的一个挑战是需要大量样本系列和相当多的资源。一个重要的考虑因素将是以临床有意义的方式解释GWAS的结果，并辨别其对所有治疗领域（包括神经系统疾病）的影响；这一挑战将需要医学和科学界的专业技能和资源。
