What question did this study set out to answer?

The research aims to validate gene-disease associations for hypertrophic cardiomyopathy using large biobanks.

March 25, 2026Journal of Personalized MedicineOpen Access

Leveraging Large and Diverse Biobanks to Evaluate Gene–Disease Associations in Hypertrophic Cardiomyopathy

View Full Paper

Ask AI

Bookmark

Why the study?

Whether large biobanks and population databases can validate ClinGen-curated gene–disease associations and provide evidence for novel gene–disease associations in HCM remained unclear.

Do rare coding variants in HCM ClinGen panel genes associate with HCM in large biobank populations?

Population

748,879 individuals across three large biobanks (All of Us, UK biobank, Mass General Brigham biobank)

Comparison

Rare coding variants in 38 genes in the HCM ClinGen panel evaluated for association with HCM

Design

Biobank-based genetic association study

Authors

SDSaif DababnehUniversity of British Columbia KOKevin OngGeneral Cardiology DYDarwin F. YeungUniversity of British Columbia

Discussion

Member takes

Implication

Supports ClinGen HCM panels for clinical variant interpretation; reinforces most definitive associations in biobanks but highlights limited sensitivity.

Key Points

The research aims to validate gene-disease associations for hypertrophic cardiomyopathy using large biobanks.
Utilized a publicly available database containing 748,879 individuals across three large biobanks.
Tested associations of rare coding variants in 38 genes from the HCM ClinGen panel with hypertrophic cardiomyopathy.
Applied Bonferroni correction to determine significance levels.
Eight out of twelve genes with definitive evidence for HCM showed nominally significant associations at a population level.
Five genes remained significant after applying Bonferroni correction, reinforcing their validity in HCM panels.
Less commonly affected genes had positively associated effect sizes but did not meet significance thresholds.

Structured PICO

Do rare coding variants in HCM ClinGen panel genes associate with HCM in large biobank populations?

Population

748,879 individuals across three large biobanks (All of Us, UK biobank, Mass General Brigham biobank)

Intervention

Rare coding variants in 38 genes in the HCM ClinGen panel

Outcome

Association with Hypertrophic Cardiomyopathy (HCM)

Large biobanks generally recapitulate established gene-disease associations for HCM, supporting ClinGen curations, though with limited sensitivity for less commonly affected genes.

Limitations

may have limited sensitivity
should not be solely relied on

Cite This Study

Dababneh et al. (2026) studied this question.

synapsesocial.com/papers/69c37b54b34aaaeb1a67dab1 https://doi.org/10.3390/jpm16030171

Topics

Hypertrophic cardiomyopathy

View Full Paper

Ask AI

Bookmark

Implication

Supports ClinGen HCM panels for clinical variant interpretation; reinforces most definitive associations in biobanks but highlights limited sensitivity.

Leveraging Large and Diverse Biobanks to Evaluate Gene–Disease Associations in Hypertrophic Cardiomyopathy

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Topics

Leveraging Large and Diverse Biobanks to Evaluate Gene–Disease Associations in Hypertrophic Cardiomyopathy

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Also Consider

Topics

Also Consider