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Title: Family history assessment significantly enhances delivery of precision medicine in the genomics era
Authors: Bylstra, Yasmin
Lim, Weng Khong 
Kam, Sylvia
Tham, Koei Wan 
Wu, R. Ryanne
Teo, Jing Xian 
Davila, Sonia 
Kuan, Jyn Ling 
Chan, Sock Hoai 
Bertin, Nicolas
Yang, Cheng Xi
Rozen, Steve 
Teh, Bin Tean 
Yeo, Khung Keong 
Cook, Stuart Alexander 
Jamuar, Saumya Shekhar 
Ginsburg, Geoffrey S.
Orlando, Lori A.
Tan, Patrick 
Keywords: Cancer
Clinically actionable variants
Family history
Population genomics screening
Issue Date: 7-Jan-2021
Publisher: BioMed Central Ltd
Citation: Bylstra, Yasmin, Lim, Weng Khong, Kam, Sylvia, Tham, Koei Wan, Wu, R. Ryanne, Teo, Jing Xian, Davila, Sonia, Kuan, Jyn Ling, Chan, Sock Hoai, Bertin, Nicolas, Yang, Cheng Xi, Rozen, Steve, Teh, Bin Tean, Yeo, Khung Keong, Cook, Stuart Alexander, Jamuar, Saumya Shekhar, Ginsburg, Geoffrey S., Orlando, Lori A., Tan, Patrick (2021-01-07). Family history assessment significantly enhances delivery of precision medicine in the genomics era. Genome Medicine 13 (1) : 3. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Background: Family history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs rendering the value of family history unknown. We evaluated the utility of incorporating family history information for genomic sequencing selection. Methods: To ascertain the relationship between family histories on such population-level initiatives, we analysed whole genome sequences of 1750 research participants with no known pre-existing conditions, of which half received comprehensive family history assessment of up to four generations, focusing on 95 cancer genes. Results: Amongst the 1750 participants, 866 (49.5%) had high-quality standardised family history available. Within this group, 73 (8.4%) participants had an increased family history risk of cancer (increased FH risk cohort) and 1 in 7 participants (n = 10/73) carried a clinically actionable variant inferring a sixfold increase compared with 1 in 47 participants (n = 17/793) assessed at average family history cancer risk (average FH risk cohort) (p = 0.00001) and a sevenfold increase compared to 1 in 52 participants (n = 17/884) where family history was not available (FH not available cohort) (p = 0.00001). The enrichment was further pronounced (up to 18-fold) when assessing only the 25 cancer genes in the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes. Furthermore, 63 (7.3%) participants had an increased family history cancer risk in the absence of an apparent clinically actionable variant. Conclusions: These findings demonstrate that the collection and analysis of comprehensive family history and genomic data are complementary and in combination can prioritise individuals for genomic analysis. Thus, family history remains a critical component of health risk assessment, providing important actionable data when implementing genomics screening programs. Trial registration: NCT02791152. Retrospectively registered on May 31, 2016. © 2021, The Author(s).
Source Title: Genome Medicine
ISSN: 1756-994X
DOI: 10.1186/s13073-020-00819-1
Rights: Attribution 4.0 International
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