Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank

J Med Genet. 2019 Mar;56(3):131-138. doi: 10.1136/jmedgenet-2018-105477. Epub 2018 Oct 20.


Background: Genomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. The UK Biobank allows us to study the medical consequences of CNVs in middle and old age in half a million well-phenotyped adults.

Methods: We analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications. After array quality control and exclusion of first-degree relatives, we compared 381 452 participants of white British or Irish origin who carried no CNVs with carriers of each of the 54 CNVs (ranging from 5 to 2843 persons). We used logistic regression analysis to estimate the risk of developing 58 common medical phenotypes (3132 comparisons).

Results and conclusions: Many of the CNVs have profound effects on medical health and mortality, even in people who have largely escaped early neurodevelopmental outcomes. Forty-six CNV-phenotype associations were significant at a false discovery rate threshold of 0.1, all in the direction of increased risk. Known medical consequences of CNVs were confirmed, but most identified associations are novel. Deletions at 16p11.2 and 16p12.1 had the largest numbers of significantly associated phenotypes (seven each). Diabetes, hypertension, obesity and renal failure were affected by the highest numbers of CNVs. Our work should inform clinicians in planning and managing the medical care of CNV carriers.

Keywords: UK biobank; cnv; medical.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biological Specimen Banks
  • DNA Copy Number Variations*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neurodevelopmental Disorders / epidemiology*
  • Neurodevelopmental Disorders / genetics
  • Odds Ratio
  • Phenotype
  • Population Surveillance
  • Quality Control
  • United Kingdom / epidemiology