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Blood pressure gene scores show tissue-linked differences

An observational analysis of 411,463 UK Biobank participants found distinct blood pressure and cardiovascular disease associations after splitting genetic scores by tissue.

Paper by Yihe Yang, Dongwon Lee, Aravinda Chakravarti, Xiaofeng Zhu · Case Western Reserve University
Fig. 1. Overview of the analysis pipeline.
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Fig. 1. Overview of the analysis pipeline.Overview of the analysis pipeline.Yang et al.

Our read

Biomarkers
Studied:
Preprint: cohort study of 411,463 European ancestry individuals
What changed:
Blood pressure effects of partitioned polygenic risk scores differed across tissue-specific regulatory elements
In the record:
The 14th paper on antihypertensive medication with results in people; 32 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
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An observational study analyzed genetic data from 411,463 UK Biobank participants of European ancestry; sample sizes varied by outcome. Researchers divided polygenic risk scores—measures combining many genetic variants—according to DNA regions that regulate gene activity in four tissues: adrenal gland, artery, heart and kidney.

The resulting components differed in their associations with blood pressure and cardiovascular disease. The authors attributed this variation to interactions between genetic variants and environmental factors, including blood pressure medication use. Models incorporating these interactions improved prediction compared with a single overall score. For validation, researchers selected 98,833 All of Us participants of European ancestry aged 40–75, then excluded those missing required information. This independent analysis reproduced the differing associations.

Why it matters

For cardiovascular disease, an important threat to health in later life, the framework may help researchers investigate how inherited risk varies with medication use.

Caveats

The observational design cannot establish that medication caused the different genetic associations. This preprint has not been peer-reviewed, and the main analyses focused on people of European ancestry.

From the paper

Participants

We further randomly removed one individual from each pair with a kinship coefficient greater than 0.0884, resulting in a total of 411,463 participants.

Methods, UK biobank (UKB)

Result

Notably, the K-tcPRS of BP_plei had an odds ratio 2.59 (95% CI: 2.18–3.08) on HTN, but it had protective effects on coronary artery disease (CAD) (OR: 0.589, 95% CI: 0.424–0.819) and myocardial infarction (MI) (OR: 0.576, 95% CI: 0.398–0.833) (Supplementary Table 8).

Results, Heterogeneity of BP tcPRS effects on cardiovascular disease (CVD) reveals interaction with antihypertension medication

Quoted word for word from the full text on PubMed Central.

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