Show Notes
Katzourou IK et al., The American Journal of Human Genetics - Population analysis of ~459,000 UK Biobank participants shows that carriers of neurodevelopmental CNVs (ND-CNVs) have higher odds of co-occurring internalizing (depression, anxiety, somatic) and cardiometabolic conditions (hypertension, dyslipidemia, obesity, T2D, CKD). Effects are stronger for deletions than duplications, greater in females, and linked to the number of haploinsufficient genes within deletions. Key terms: copy-number variants, multimorbidity, internalizing disorders, cardiometabolic, UK Biobank.
Study Highlights:
Using CNV calls and linked EHRs in the UK Biobank, the authors tested associations between 54 ND-CNVs and combinations of internalizing and cardiometabolic conditions (ICM-MM). Aggregated ND-CNV carriers (n≈7,546; ~1.6%) had higher odds of ICM-MM (OR range 1.21–1.57) and a higher ICM-MM frequency (14.2% vs 11.5%). Deletions showed stronger effects than duplications and the number of haploinsufficient genes in deletions was associated with greater ICM-MM risk. No robust interactions were detected between ND-CNV status and polygenic risk scores after multiple testing correction.
Conclusion:
ND-CNVs increase risk of internalizing–cardiometabolic multimorbidity at the population level, especially for deletions and in females, suggesting the need for heightened clinical monitoring of carriers.
Music:
Enjoy the music based on this article at the end of the episode.
Article title:
Neurodevelopmental copy-number variants increase risk of internalizing and cardiometabolic multimorbidity: Findings from the UK Biobank
First author:
Katzourou IK
Journal:
The American Journal of Human Genetics
DOI:
10.1016/j.ajhg.2026.02.021
Reference:
Katzourou IK, LINC consortium, Barroso I, et al. Neurodevelopmental copy-number variants increase risk of internalizing and cardiometabolic multimorbidity: Findings from the UK Biobank. The American Journal of Human Genetics. 2026;113:1–11. https://doi.org/10.1016/j.ajhg.2026.02.021
License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/
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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-04-08.
QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited transcript sections covering ND-CNV–ICM-MM association, UK Biobank design and CNV calling, dosage-sensitivity (haploinsufficient vs triplosensitive), deletion vs duplication effects (notably 16p11.2), sex differences, PRS interaction analyses, and clinical implications including multidisciplinary care and casca
- transcript topics: Definition of ND-CNVs and ICM-MM; UK Biobank cohort size, CNV calling methods (PennCNV); Dosage sensitivity: haploinsufficient vs triplosensitive genes; Deletion vs duplication effects on ICM-MM and obesity; 16p11.2 region emphasis; Sex differences in ND-CNV associations
QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0
Metadata Audited:
- article_doi
- article_title
- article_journal
- license
Factual Items Audited:
- ND-CNVs increase risk of internalizing–cardiometabolic multimorbidity (ICM-MM) in UK Biobank with OR 1.21–1.57 and 14.2% vs 11.5% prevalence
- Deletions show stronger effects than duplications; 16p11.2 region deletions are notable
- The number of haploinsufficient genes within deletions is associated with higher ICM-MM; duplications' triplosensitive genes do not show the same pattern
- No robust ND-CNV × PRS interactions after multiple-testing correction; nominal interactions present in some PRS analyses
- Sex differences: higher risk in females for certain ND-CNV associations (e.g., T2D, internalizing)
- Survival bias in UK Biobank implies observed effect sizes are conservative lower bounds
QC result: Pass.
