RT Journal Article
SR Electronic
T1 Family History Assessment Significantly Enhances Delivery of Precision Medicine in the Genomics Era
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.29.926139
DO 10.1101/2020.01.29.926139
A1 Yasmin Bylstra
A1 Weng Khong Lim
A1 Sylvia Kam
A1 Koei Wan Tham
A1 R. Ryanne Wu
A1 Jing Xian Teo
A1 Sonia Davila
A1 Jyn Ling Kuan
A1 Sock Hoai Chan
A1 Nicolas Bertin
A1 ChengXi Yang
A1 Steve Rozen
A1 Bin Tean Teh
A1 Khung Keong Yeo
A1 Stuart Alexander Cook
A1 Lori A. Orlando
A1 Saumya Shekhar Jamuar
A1 Geoffrey S. Ginsburg
A1 Patrick Tan
YR 2020
UL http://biorxiv.org/content/early/2020/01/30/2020.01.29.926139.abstract
AB 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, with less emphasis on family history assessment. We evaluated the utility of family history for genomic sequencing selection.Methods We analysed whole genome sequences of 1750 healthy research participants, with and without preselection based on standardised family history collection, screening 95 cancer genes.Results The frequency of likely pathogenic/ pathogenic (LP/P) variants in 884 participants with no family history available (FH not available group) (2%) versus 866 participants with family history available (FH available group) (3.1%) was not significant (p=0.158). However, within the FH available group, amongst 73 participants with an increased family history cancer risk (increased FH risk), 1 in 7 participants carried a LP/P variant inferring a six-fold increase compared with 1 in 47 participants assessed at average family history cancer risk (average FH risk) and a seven-fold increase compared to the FH not available group. The enrichment was further pronounced (up to 18-fold) when assessing the 25 cancer genes in the ACMG 59-gene panel. Furthermore, 63 participants had an increased family history cancer risk in absence of an apparent LP/P variant.Conclusion Our findings show that systematic family history collection remains critical for health risk assessment, providing important actionable data and augmenting the yield from genomic data. Family history also highlights the potential impact of additional hereditary, environmental and behavioural influences not reflected by genomic sequencing.