Circulation Genomic and Precision MedicineNov 5, 2026, 10:59 GMT

Genetics linked to risks at “good” cholesterol extremes

In UK Biobank, genetically unexpected low “good” cholesterol carried a relative cardiovascular disease rate of 1.20 versus genetically consistent low levels.

Paper by Elad Shemesh, Keona Ka Ying Pang, Pascal B. Meyre, +9Guillaume Paré · Thrombosis and Atherosclerosis Research Institute

An opened artery narrowed by fatty deposits sits beside a smaller, clearer artery, sparse cholesterol particles, and groups of upright figures.

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Populations

Studied:: Cohort study of European-ancestry participants at HDL cholesterol extremes
What changed:: Cardiovascular disease risk was higher with genetically unexpected versus genetically consistent low HDL in UK Biobank (hazard ratio 1.20)
The catch:: Non-genetic influences on cholesterol could also drive disease and mortality differences between genetic-discordance groups
Why it’s aging research:: It bears on staying healthy in midlife and later life.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper

UK Biobank participants (408,353) and All of Us participants (115,423) had no cardiovascular disease caused by fatty buildup in arteries when they entered this observational study. Researchers examined high-density lipoprotein (HDL) cholesterol, often called “good” cholesterol. A score based on 247 genetic variants identified European-ancestry participants whose extreme cholesterol levels matched or contradicted their genetic predisposition.

Extremely low HDL cholesterol was linked to higher cardiovascular disease and mortality across ancestries in both cohorts. Among European-ancestry participants, genetically unexpected low levels carried higher risks than genetically consistent low levels. Extremely high HDL cholesterol was linked to higher mortality among UK Biobank participants of European ancestry, but not their All of Us counterparts. In UK Biobank, that association was confined to people whose high levels contradicted their genetic predisposition.

Why it matters

For age-related cardiovascular disease, the findings suggest that risk assessment based on extreme cholesterol levels may need to consider genetic predisposition, ancestry and region.

Caveats

People whose cholesterol contradicted their genetic predisposition may also have differed in other ways that affected disease and mortality. The genetic comparisons covered only participants of European ancestry.