AgingResearch.NewsJoin free
Journal of Medical Genetics

DNA study finds new links to inherited heart muscle disease

Among 411,213 UK Biobank participants, the score’s top 5% was linked to higher diagnosis risk than the lower 95%, with a hazard ratio of 3.19.

Paper by Luís Rocha Lopes, Nay Aung, Stefan van Duijvenboden, +17 more authorsPerry Mark Elliott · St Bartholomew's Hospital
Figure 1 from Journal of Medical Genetics
Open the figure at full size
Figure 1. Lopes et al.

Our read

Biomarkers
Studied:
Meta-analysis of people with hypertrophic cardiomyopathy and controls, against controls
What changed:
Comparing people with hypertrophic cardiomyopathy against controls identified 70 associated genetic regions, including four new ones
The catch:
Differences in case identification across cohorts could distort individual genetic associations
In the record:
The 139th paper on polygenic risk score with results in people; 456 on record in all.
Why it’s aging research:
It bears on staying healthy in midlife and later life.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
Follow @agingbrief

An observational genetic study compared 2,284 people of European ancestry with hypertrophic cardiomyopathy, an inherited disease involving thickened heart muscle, with 4,525 controls. The affected group averaged 54.0 years old, and 65% were men. Researchers combined their results with published genetic data in two pooled analyses. These identified 70 DNA regions associated with the disease, including four newly associated regions.

The researchers built a polygenic risk score, which combines information from many genetic variants. They tested its association with diagnosis in 411,213 UK Biobank participants. Scores in the top 5% were associated with higher diagnosis risk than scores in the lower 95%. The hazard ratio of 3.19 described relative, not absolute, risk. Among participants without the disease, higher scores were also linked to thicker walls in the heart’s main pumping chamber.

Why it matters

Inherited heart muscle disease has widely varying effects and outcomes. Understanding its genetic contributors may inform risk assessment for heart health over time, rather than biological aging itself.

Caveats

These observational associations do not establish causation or show that using the score improves care. The discovery sample had European ancestry, limiting what those findings establish for other ancestry groups.

From the paper

Participants

The discovery GWAS comprised 6809 European individuals of whom 2284 were HCM cases and 4525 were EXCEED study controls.

Results

Result

The third discovery locus, PPP1R3A, reached nominal significance in the single-trait meta-analysis (OR=1.12, 95% CI 1.06 to 1.19, pdiscovery=2.75×10−10, pmeta=8.0×10−5), with significant heterogeneity (Q p<0.05).

Results, Meta-analysis with recent Tadros et al dataset

Limitation

While we identified novel loci, significant heterogeneity across cohorts used for the meta-analysis reduced the reliability of some signals.

Limitations and implications for future work

Quoted word for word from the full text on jmg.bmj.com.

Comments

Be the first to comment.

More on Human genetics