JAMA:健康人有必要做疾病基因筛查吗?
2016/01/09
美国医学会杂志(JAMA)的一份报告称潜在的有害的遗传变异并不总会变成本身有障害的。该报告给当今的热潮浇了瓢凉水,告诉我们基因检测是必须谨慎而行。


由于涉及高科技,又只需要少量血样即可对被检者进行DNA分析,基因检测成了一个时髦的词。想看看自己有没有易病基因,看看未出生的宝宝有没有遗传缺陷。很多人都希望做一下检测。基因测序也成了如今投资的热点。如果你像安吉丽娜•朱莉那样检查出BRCA1基因缺陷,是不是也要去切除乳腺和卵巢呢?健康的人到底有没有必要去做疾病基因筛查呢?

最新的研究报告给当今的热潮浇了瓢凉水,告诉我们基因检测是必须谨慎而行。

你的基因是你的命运吗?据美国医学会杂志(JAMA)的一份报告称,不一定。这项研究的底线:有条件的证据证明在一般人群中,只有一小部分的基因变异与长QT综合征或Brugada综合征(两个致命的心律问题)相关的。换句话说,有一个潜在的有害的遗传变异并不总会变成本身有障害的。更糟糕的是,三个实验室做测试在那种变异是有害的方面不一致。

这份JAMA的研究结果,做为电子医疗记录和基因组(eMERGE)网络的一部分,提出一个问题:怎么告诉他们自己人的基因组分析。这种测试经常用于识别一个特定的问题,如癌症相关基因与在他们的家庭有得癌症的人。但他们也可以识别其他潜在的有问题的基因变异。这些“额外的”发现被称为偶然或次要发现。

美国医学遗传学会建议医生和研究人员告诉个人超过50的作为偶然发现的基因变异,包括JAMA报告检查的两个基因。

但在新发现下这种方法仍有意义的吗?

由Vanderbilt大学的Ellen Wright Clayton认为:这些结果是惊人的。他们得考虑经常性地告诉病人关于遗传分析的二次发现问题是否明智。

二次调查结果的概念不是新的。核磁共振和核磁共振成像经常出现意外发现。当他们表现出隐藏的癌症时,它们是重要的。然而更多时,它们不提供有用的临床信息。作为遗传分析的实践的发展,如何处理次要发现正在成为一个日益重要的问题。

JAMA的研究中检测的两个基因在被认为是二次发现的范例,因为它们具有潜在的危险性心律失常有关。了解情况的存在意味着你可以采取行动,以防止致命的心脏骤停。但从这个研究的教训是,有一个Brugada或长QT综合的基因变异不一定意味着一个人有病。事实上,只有在研究中1/3的一个基因变异的人有异常心脏节律的迹象,只有百分之10的人被诊断出患有QT间期延长。

临床遗传学看已经投入了大量的精力,分离我们知道有害的或有可能导致那些我们不知道的问题的基因变异。美国医学遗传学学院已经鉴定JAMA检测的这两个基因变异是致病的。这意味着,就是如果你它们你作为病人做些准备。但现在看起来不是这样的情况。

这对新生儿或作为一部分精密医学计划的全基因组筛查有很大的影响。这样的测试将反馈有关许多遗传变异的信息。有人会告诉我们,“我们发现你基因中的这些变异可能是重要的,但我们真的不知道他们是否会让你生病或做些什么。”这将是相当混乱和可能产生不必要的恐惧。

这是一个有症状或其家庭成员有特殊情况的人群中查找基因变异,是有真正的价值。但是,在普通人群中寻找基因变异可能弊大于利。

安吉丽娜•朱莉的手术也不是为了显示个性随便做的,由于家族遗传,她家中的三位女性都因此去世,母亲确诊卵巢癌时49岁。医生已经建议她在家人发病的年龄的至少十年前进行手术。所以啦,一定要相信科学,听从医嘱,不要盲目跟风哦。

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  • Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records

    Importance Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants. Objective To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes. Design, Setting, and Participants This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014. Exposures One or more variants designated as pathogenic in SCN5A or KCNH2. Main Outcomes and Measures Arrhythmia or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review. Results Among 2022 study participants (median age, 61 years [interquartile range, 56-65 years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency <0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen κ = 0.26). An ICD-9 code for arrhythmia was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, −5% to +13%; P = .35). In the 1270 (63%) with ECGs, corrected QT intervals were not different in variant carriers vs those without (median, 429 vs 439 milliseconds; difference, −10 milliseconds; 95% CI, −16 to +3 milliseconds; P = .17). After manual review, 22 of 63 participants (35%) with designated variants had any ECG or arrhythmia phenotype, and only 2 had corrected QT interval longer than 500 milliseconds. Conclusions and Relevance Among laboratories experienced in genetic testing for cardiac arrhythmia disorders, there was low concordance in designating SCN5A and KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying patients of incidental genetic findings.

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