Penetrance and outcomes at 1-year following return of actionable variants identified by genome sequencing.
Penetrance and outcomes at 1-year following return of actionable variants identified by genome sequencing.
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DOI：
10.1038/s41436-021-01142-9
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发表时间：
2021-07
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影响因子：
--
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我们估计了可操作的遗传变异的发生率，并评估了结果返回（RoR）后的近期结果。高胆固醇血症和/或结肠息肉的参与者（n=2535）进行了68个基因和14个单核苷酸变异的靶向测序。外显率是根据电子健康记录（EHR）中相关特征的存在来估计的。通过EHR审查确定RoR 1年内发生的结局。分析按第1层和非第1层疾病分层。在122人中发现了可采取行动的结果，并向98人披露了结果。1级疾病变异体的平均患病率（67%; n=58人）高于非1级变异体（46.5%; n=58人）。在排除了45个人之后（死亡者、无应答者、已知遗传诊断、嵌合体），RoR后77名参与者中有83%观察到≥1个结局; 77.9%有过程结局（转诊至专科医生、新检测、启动监测）; 67.9%有中间结局（新的检查结果或诊断）; 19.2%有临床结局（治疗调整，风险降低手术）。风险降低手术发生在第1层的参与者比非第1层变异的参与者更频繁。在RoR后的一年中，在57%的参与者中观察到相关的表型特征，而在19.2%的参与者中发生了临床结局。
We estimated penetrance of actionable genetic variants and assessed near-term outcomes following return of results (RoR). Participants (n=2535) with hypercholesterolemia and/or colon polyps underwent targeted sequencing of 68 genes and 14 single nucleotide variants. Penetrance was estimated based on presence of relevant traits in the electronic health record (EHR). Outcomes occurring within 1-year of RoR were ascertained by EHR review. Analyses were stratified by Tier 1 and non-Tier 1 disorders. Actionable findings were present in 122 individuals and results were disclosed to 98. The average penetrance for Tier 1 disorder variants (67%; n=58 individuals) was higher than in non-Tier 1 variants (46.5%; n=58 individuals). After excluding 45 individuals (decedents, non-responders, known genetic diagnoses, mosaicism), ≥1 outcomes were noted in 83% of 77 participants following RoR; 77.9% had a process outcome (referral to a specialist, new testing, surveillance initiated); 67.9% had an intermediate outcome (new test finding or diagnosis); 19.2% had a clinical outcome (therapy modified, risk reduction surgery). Risk reduction surgery occurred more often in participants with Tier 1 than those with non-Tier 1 variants. Relevant phenotypic traits were observed in 57% whereas a clinical outcome occurred in 19.2% of participants with actionable genomic variants in the year following RoR.
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影响因子：
3.7
作者：
McMurry AJ;Murphy SN;MacFadden D;Weber G;Simons WW;Orechia J;Bickel J;Wattanasin N;Gilbert C;Trevvett P;Churchill S;Kohane IS
通讯作者：
Kohane IS
影响因子：
37.8
作者：
Hosseini SM;Kim R;Udupa S;Costain G;Jobling R;Liston E;Jamal SM;Szybowska M;Morel CF;Bowdin S;Garcia J;Care M;Sturm AC;Novelli V;Ackerman MJ;Ware JS;Hershberger RE;Wilde AAM;Gollob MH;National Institutes of Health Clinical Genome Resource Consortium
通讯作者：
National Institutes of Health Clinical Genome Resource Consortium
影响因子：
5.3
作者：
Doble, Brett;Schofield, Deborah J.;Mattick, John S.
通讯作者：
Mattick, John S.
影响因子：
5.2
作者：
Haer-Wigman, Lonneke;van der Schoot, Vyne;Yntema, Helger G.
通讯作者：
Yntema, Helger G.
影响因子：
24.5
作者：
Møller P;Seppälä T;Bernstein I;Holinski-Feder E;Sala P;Evans DG;Lindblom A;Macrae F;Blanco I;Sijmons R;Jeffries J;Vasen H;Burn J;Nakken S;Hovig E;Rødland EA;Tharmaratnam K;de Vos Tot Nederveen Cappel WH;Hill J;Wijnen J;Green K;Lalloo F;Sunde L;Mints M;Bertario L;Pineda M;Navarro M;Morak M;Renkonen-Sinisalo L;Frayling IM;Plazzer JP;Pylvanainen K;Sampson JR;Capella G;Mecklin JP;Möslein G;Mallorca Group (http://mallorca-group.eu)
通讯作者：
Mallorca Group (http://mallorca-group.eu)