Genome-wide association studies of schizophrenia: does bigger lead to better results?
Genome-wide association studies of schizophrenia: does bigger lead to better results?
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DOI：
10.1097/yco.0b013e32835035dd
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发表时间：
2012-03
影响因子：
6.9
通讯作者：
Petryshen TL
中科院分区：
文献类型：
--
作者：
Bergen SE;Petryshen TL
在过去的六年里，已经发表了许多关于精神分裂症的全基因组关联研究(GWAS)，在过去的一年中发表了一些关键报告。这些研究的规模已经从小的个体样本发展到大型的合作努力。这篇综述旨在批判性地评估随着遗传关联研究的样本量和规模的增长，结果是否有所改善。基因组基因分型和精神分裂症相关性研究样本量的增加导致了具有很高统计置信度的风险基因数量的平行增加。在一项研究中，近20个基因或基因座超过了全基因组的显著阈值(p=5×10−8)，并且有几个基因或基因座在多个GWA中重复。识别复杂疾病的遗传基础有助于深入了解导致疾病表现的病因学机制。精神分裂症迫切需要新的、更有效的治疗方法，随着我们对相关基因的了解，针对相关生物过程的能力也在增长。随着GWAS样本大小的增加，更多的基因被高度自信地识别出来，开始为这种疾病的病因和病理生理学基础提供洞察力。
Numerous genome-wide association studies (GWAS) of schizophrenia have been published in the past six years, with a number of key reports published in the last year. The studies have evolved in scale from small individual samples to large collaborative endeavors. This review aims to critically assess whether the results have improved as the sample size and scale of genetic association studies has grown. Genomic genotyping and increasing sample sizes for schizophrenia association studies has led to parallel increases in the number of risk genes discovered with high statistical confidence. Nearly 20 genes or loci have surpassed the genome-wide significance threshold (p = 5 × 10−8) in a single study, and several have been replicated in more than one GWAS. Identifying the genetic underpinnings of complex diseases offers insight into the etiological mechanisms leading to manifestation of the disease. New and more effective treatments for schizophrenia are desperately needed, and the ability to target the relevant biological processes grows with our understanding of the genes involved. As the size of GWAS samples has increased, more genes have been identified with high confidence that have begun to provide insight into the etiological and pathophysiological foundations of this disorder.