Khoury Muin J, Bertram Lars, Boffetta Paolo, Butterworth Adam S, Chanock Stephen J, Dolan Siobhan M, Fortier Isabel, Garcia-Closas Montserrat, Gwinn Marta, Higgins Julian P T, Janssens A Cecile J W, Ostell James, Owen Ryan P, Pagon Roberta A, Rebbeck Timothy R, Rothman Nathaniel, Bernstein Jonine L, Burton Paul R, Campbell Harry, Chockalingam Anand, Furberg Helena, Little Julian, O'Brien Thomas R, Seminara Daniela, Vineis Paolo, Winn Deborah M, Yu Wei, Ioannidis John P A
Office of Public Health Genomics, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Am J Epidemiol. 2009 Aug 1;170(3):269-79. doi: 10.1093/aje/kwp119. Epub 2009 Jun 4.
Genome-wide association studies (GWAS) have led to a rapid increase in available data on common genetic variants and phenotypes and numerous discoveries of new loci associated with susceptibility to common complex diseases. Integrating the evidence from GWAS and candidate gene studies depends on concerted efforts in data production, online publication, database development, and continuously updated data synthesis. Here the authors summarize current experience and challenges on these fronts, which were discussed at a 2008 multidisciplinary workshop sponsored by the Human Genome Epidemiology Network. Comprehensive field synopses that integrate many reported gene-disease associations have been systematically developed for several fields, including Alzheimer's disease, schizophrenia, bladder cancer, coronary heart disease, preterm birth, and DNA repair genes in various cancers. The authors summarize insights from these field synopses and discuss remaining unresolved issues -- especially in the light of evidence from GWAS, for which they summarize empirical P-value and effect-size data on 223 discovered associations for binary outcomes (142 with P < 10(-7)). They also present a vision of collaboration that builds reliable cumulative evidence for genetic associations with common complex diseases and a transparent, distributed, authoritative knowledge base on genetic variation and human health. As a next step in the evolution of Human Genome Epidemiology reviews, the authors invite investigators to submit field synopses for possible publication in the American Journal of Epidemiology.
全基因组关联研究（GWAS）使得常见基因变异和表型的可用数据迅速增加，并发现了许多与常见复杂疾病易感性相关的新基因座。整合GWAS和候选基因研究的证据，需要在数据生成、在线发表、数据库开发以及持续更新的数据综合分析等方面共同努力。本文作者总结了在这些方面的当前经验和挑战，这些内容在2008年由人类基因组流行病学网络主办的多学科研讨会上进行了讨论。针对包括阿尔茨海默病、精神分裂症、膀胱癌、冠心病、早产以及各种癌症中的DNA修复基因等多个领域，系统地开发了整合许多已报道基因-疾病关联的综合领域综述。作者总结了这些领域综述的见解，并讨论了尚未解决的问题——特别是根据GWAS的证据，为此他们总结了223个已发现的二元结局关联（142个P < 10⁻⁷）的经验P值和效应大小数据。他们还提出了一种合作愿景，即建立关于常见复杂疾病基因关联的可靠累积证据，以及一个关于基因变异与人类健康的透明、分布式、权威知识库。作为人类基因组流行病学综述发展的下一步，作者邀请研究人员提交领域综述，以便有可能在美国《流行病学杂志》上发表。
