Ramos Erin M, Din-Lovinescu Corina, Berg Jonathan S, Brooks Lisa D, Duncanson Audrey, Dunn Michael, Good Peter, Hubbard Tim J P, Jarvik Gail P, O'Donnell Christopher, Sherry Stephen T, Aronson Naomi, Biesecker Leslie G, Blumberg Bruce, Calonge Ned, Colhoun Helen M, Epstein Robert S, Flicek Paul, Gordon Erynn S, Green Eric D, Green Robert C, Hurles Matthew, Kawamoto Kensaku, Knaus William, Ledbetter David H, Levy Howard P, Lyon Elaine, Maglott Donna, McLeod Howard L, Rahman Nazneen, Randhawa Gurvaneet, Wicklund Catherine, Manolio Teri A, Chisholm Rex L, Williams Marc S
Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):93-104. doi: 10.1002/ajmg.c.31386. Epub 2014 Mar 13.
Genome-wide association studies, DNA sequencing studies, and other genomic studies are finding an increasing number of genetic variants associated with clinical phenotypes that may be useful in developing diagnostic, preventive, and treatment strategies for individual patients. However, few variants have been integrated into routine clinical practice. The reasons for this are several, but two of the most significant are limited evidence about the clinical implications of the variants and a lack of a comprehensive knowledge base that captures genetic variants, their phenotypic associations, and other pertinent phenotypic information that is openly accessible to clinical groups attempting to interpret sequencing data. As the field of medicine begins to incorporate genome-scale analysis into clinical care, approaches need to be developed for collecting and characterizing data on the clinical implications of variants, developing consensus on their actionability, and making this information available for clinical use. The National Human Genome Research Institute (NHGRI) and the Wellcome Trust thus convened a workshop to consider the processes and resources needed to: (1) identify clinically valid genetic variants; (2) decide whether they are actionable and what the action should be; and (3) provide this information for clinical use. This commentary outlines the key discussion points and recommendations from the workshop.
全基因组关联研究、DNA测序研究及其他基因组研究发现，越来越多与临床表型相关的基因变异，这些变异可能有助于为个体患者制定诊断、预防和治疗策略。然而，很少有变异被纳入常规临床实践。原因有多个，但两个最重要的原因是关于变异临床意义的证据有限，以及缺乏一个全面的知识库来收录基因变异、它们与表型的关联，以及其他相关的表型信息，而这些信息可供试图解读测序数据的临床团队公开获取。随着医学领域开始将基因组规模分析纳入临床护理，需要开发一些方法来收集和描述关于变异临床意义的数据，就其可操作性达成共识，并使这些信息可供临床使用。因此，美国国家人类基因组研究所（NHGRI）和惠康信托基金会召开了一次研讨会，以考虑所需的流程和资源，目的是：（1）识别具有临床有效性的基因变异；（2）确定它们是否具有可操作性以及应采取何种行动；（3）提供此信息以供临床使用。本评论概述了研讨会上的关键讨论要点和建议。
