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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bylstra, Y; Lim, WK; Kam, S; Tham, KW; Wu, RR; Teo, JX; Davila, S; Kuan, JL; Chan, SH; Bertin, N; Yang, CX; Rozen, S; Teh, BT; Yeo, KK; Cook, SA; Jamuar, SS; Ginsburg, GS; Orlando, LA; Tan, P

Published Date

  • January 7, 2021

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 3 -

PubMed ID

  • 33413596

Pubmed Central ID

  • PMC7791763

Electronic International Standard Serial Number (EISSN)

  • 1756-994X

Digital Object Identifier (DOI)

  • 10.1186/s13073-020-00819-1


  • eng

Conference Location

  • England