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. 2021 Jan 7;13(1):3.
doi: 10.1186/s13073-020-00819-1.

Family history assessment significantly enhances delivery of precision medicine in the genomics era

Yasmin Bylstra  1 , Weng Khong Lim  1   2   3 , Sylvia Kam  1   4 , Koei Wan Tham  1   5 , R Ryanne Wu  6 , Jing Xian Teo  1 , Sonia Davila  1   3   7 , Jyn Ling Kuan  1 , Sock Hoai Chan  8 , Nicolas Bertin  9 , Cheng Xi Yang  10 , Steve Rozen  1   2 , Bin Tean Teh  1   11 , Khung Keong Yeo  7   12 , Stuart Alexander Cook  1   7   12 , Saumya Shekhar Jamuar  1   3   4   13 , Geoffrey S Ginsburg  6 , Lori A Orlando  14 , Patrick Tan  15   16   17
Affiliations

Family history assessment significantly enhances delivery of precision medicine in the genomics era

Yasmin Bylstra et al. Genome Med. .

Erratum in

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: ClinicalTrials.gov NCT02791152 . Retrospectively registered on May 31, 2016.

Keywords: Cancer; Clinically actionable variants; Family history; Population genomics screening.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Family history assessment and clinically actionable variant detection overview
See this image and copyright information in PMC

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