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Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank
  1. Karen Crawford,
  2. Matthew Bracher-Smith,
  3. David Owen,
  4. Kimberley M Kendall,
  5. Elliott Rees,
  6. Antonio F Pardiñas,
  7. Mark Einon,
  8. Valentina Escott-Price,
  9. James T R Walters,
  10. Michael C O’Donovan,
  11. Michael J Owen,
  12. George Kirov
  1. MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
  1. Correspondence to Dr. George Kirov, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Hadyn Ellis Building,Maindy Road, Cardiff CF14 4XN, UK; kirov{at}


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.

  • cnv
  • UK biobank
  • medical
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  • Contributors KC, MB-S and DO analysed the data; KMK, ER and MB-S called the CNVs; AFP and ME contributed to the bioinformatics and website design; VE-P, JTRW, MCO’D and MJO contributed to the statistical analysis; JTRW, MCO’D and MJO edited the paper; GK conceived the project, drafted the paper and took part in all analysis steps.

  • Funding The work at Cardiff University was funded by the Medical Research Council (MRC) Centre Grant (MR/L010305/1) and Programme Grant (G0800509).

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Ethical approval for the study was granted by the North West multi-centre ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All CNV calls will be made available to the UK Biobank, in accordance with their requirements, within 6 months of the first publication of results.

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