Incidentalome from Genomic Sequencing: A Barrier to Personalized Medicine?

被引：16

作者：

Jamuar, Saumya Shekhar ^{[1
,2
]}

Kuan, Jyn Ling ^{[3
,8
]}

Brett, Maggie ^{[4
]}

Tiang, Zenia ^{[3
,8
]}

Tan, Wilson Lek Wen ^{[3
,8
]}

Lim, Jiin Ying ^{[1
]}

Liew, Wendy Kein Meng ^{[1
,2
]}

Javed, Asif ^{[3
]}

Liew, Woei Kang ^{[1
]}

Law, Hai Yang ^{[1
,2
]}

Tan, Ee Shien ^{[1
,2
]}

Lai, Angeline ^{[1
,2
]}

Ng, Ivy ^{[1
,2
]}

Teo, Yik Ying ^{[5
]}

Venkatesh, Byrappa ^{[6
]}

Reversade, Bruno ^{[7
]}

Tan, Ene Choo ^{[4
]}

Foo, Roger ^{[3
,8
]}

机构：

[1] KK Womens & Childrens Hosp, Dept Paediat, Singapore, Singapore

[2] Singhlth Duke NUS Grad Med Sch, Paediat Acad Clin Programme, Singapore, Singapore

[3] ASTAR, Genome Inst Singapore, Singapore, Singapore

[4] KK Womens & Childrens Hosp, KK Res Ctr, Singapore, Singapore

[5] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore

[6] ASTAR, Inst Mol & Cell Biol, Singapore, Singapore

[7] ASTAR, Inst Med Biol, Singapore, Singapore

[8] Natl Univ Singapore, Natl Univ Hlth Syst, Cardiovasc Res Inst, Singapore 117548, Singapore

来源：

EBIOMEDICINE | 2016年 / 5卷

基金：

英国医学研究理事会;

关键词：

Incidental findings; Genomic sequencing; Personalized medicine; MOLECULAR-PATHOLOGY; BREAST-CANCER; EXOME; RECOMMENDATIONS; RETURN; PARTICIPANTS; GENETICS; BRCA1; SURVEILLANCE; ASSOCIATION;

D O I：

10.1016/j.ebiom.2016.01.030

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: In Western cohorts, the prevalence of incidental findings (IFs) or incidentalome, referring to variants in genes that are unrelated to the patient's primary condition, is between 0.86% and 8.8%. However, data on prevalence and type of IFs in Asian population is lacking. Methods: In 2 cohorts of individuals with genomic sequencing performed in Singapore (total n = 377), we extracted and annotated variants in the 56 ACMG-recommended genes and filtered these variants based on the level of pathogenicity. We then analyzed the precise distribution of IFs, class of genes, related medical conditions, and potential clinical impact. Results: We found a total of 41,607 variants in the 56 genes in our cohort of 377 individuals. After filtering for rare and coding variants, we identified 14 potential variants. After reviewing primary literature, only 4 out of the 14 variants were classified to be pathogenic, while an additional two variants were classified as likely pathogenic. Overall, the cumulative prevalence of IFs (pathogenic and likely pathogenic variants) in our cohort was 1.6%. Conclusion: The cumulative prevalence of IFs through genomic sequencing is low and the incidentalome may not be a significant barrier to implementation of genomics for personalized medicine. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：211 / 216

页数：6

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