1 in 38 individuals at risk of a dominant medically actionable disease

Lonneke Haer-Wigman, Vyne van der Schoot, Ilse Feenstra, Anneke T. Vulto-van Silfhout, Christian Gilissen, Han G. Brunner, Lisenka E. L. M. Vissers, Helger G. Yntema*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Clinical genomic sequencing can identify pathogenic variants unrelated to the initial clinical question, but of medical relevance to the patients and their families. With ongoing discussions on the utility of disclosing or searching for such variants, it is of crucial importance to obtain unbiased insight in the prevalence of these incidental or secondary findings, in order to better weigh potential risks and benefits. Previous studies have reported a broad range of secondary findings ranging from 1 to 9%, merely attributable to differences in study design, cohorts tested, sequence technology used and genes analyzed. Here, we analyzed WES data of 1640 anonymized healthy Dutch individuals to establish the frequency of medically actionable disease alleles in an outbred population of European descent. Our study shows that 1 in 38 healthy individuals (2.7%) has a (likely) pathogenic variant in one of 59 medically actionable dominant disease genes for which the American College of Medical Genetics and Genomics (ACMG) recommends disclosure. Additionally, we identified 36 individuals (2.2%) to be a carrier of a recessive pathogenic disease allele. Whereas these frequencies of secondary findings are in line with what has been reported in the East-Asian population, the pathogenic variants are differently distributed across the 59 ACMG genes. Our results contribute to the debate on genetic risk factor screening in healthy individuals and the discussion whether the potential benefits of this knowledge and related preventive options, outweigh the risk of the emotional impact of the test result and possible stigmatization.

Original languageEnglish
Pages (from-to)325-330
Number of pages6
JournalEuropean Journal of Human Genetics
Volume27
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • INCIDENTAL FINDINGS
  • SECONDARY FINDINGS
  • SEQUENCE VARIANTS
  • AMERICAN-COLLEGE
  • CLINICAL EXOME
  • RECOMMENDATIONS
  • GENETICS

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