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Public evidence
Homo sapiensPCSK9

What does naturally occurring PCSK9 loss of function tell us about an editing target?

Change

Naturally inherited PCSK9 variants; no editing intervention.

Measured

Mean LDL cholesterol and coronary heart disease incidence.

Observed outcome

In ARIC, 2.6% of 3,363 Black participants carried PCSK9 nonsense variants; carriers had 28% lower mean LDL cholesterol than noncarriers.

Source 1
System
Homo sapiens · ARIC study participants; published population groups
Setting
Observational ARIC comparison over 15 years.
Comparison
Participants without the studied variants in the corresponding population groups.

What was observed

Checked findings go into your research brief.

3
ObservedSource 1

In ARIC, 2.6% of 3,363 Black participants carried PCSK9 nonsense variants; carriers had 28% lower mean LDL cholesterol than noncarriers.

Abstract: Results, first population comparison

Measurement details
Reported value
28 % lower mean LDL cholesterol
Group
Nonsense-variant carriers versus noncarriers among 3,363 Black participants
ObservedSource 1

In the ARIC Black-participant group, PCSK9 nonsense-variant carriers versus noncarriers had a CHD hazard ratio of 0.11 (95% CI 0.02–0.81).

Abstract: Results, first population comparison

Measurement details
Reported value
0.11 hazard ratio
Group
PCSK9 nonsense-variant carriers versus noncarriers in the ARIC Black-participant group
Reported interval
95% confidence interval: 0.02 to 0.81
ObservedSource 1

In ARIC, 3.2% of 9,524 White participants carried a PCSK9 variation associated with 15% lower LDL cholesterol and a CHD hazard ratio of 0.50 (95% CI 0.32–0.79) versus noncarriers.

Abstract: Results, second population comparison

Measurement details
Reported value
0.5 hazard ratio
Group
PCSK9 variant carriers versus noncarriers in the ARIC White-participant group
Reported interval
95% confidence interval: 0.32 to 0.79

What this supports

Interpretation
  • The findings support investigating PCSK9 reduction.
What this does not establish
  • Inherited lifelong exposure does not establish the benefit, safety, or effect size of editing later in life.
Gene location & edit specificity

No exact edit interval established by this evidence review.

Same gene, different setting

Compare the contexts before carrying a finding across them.

PCSK9: what VERVE-102 measuredHomo sapiens · Adults with heterozygous familial hypercholesterolemia or premature coronary artery disease

Sources

Reviewed Sep 26, 2026
1Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease2006 · Peer-reviewed observational study
Reviewed
Abstract only
Sections
Abstract: Methods · Abstract: Results
DOI
10.1056/NEJMoa054013
We compared the incidence of CHD
Abstract: Methods
Read the source