27 October 2025

GENinCode Plc

("GENinCode" or the "Company")

Publication of Landmark Study in JACC: Advances

Validation of CARDIO inCode-Score® for improved coronary heart disease risk prediction

GENinCode Plc (AIM: GENI), the predictive genetics company focused on the prevention of cardiovascular disease ("CVD") and risk assessment of ovarian cancer, announces the publication of a major clinical study in JACC: Advances evaluating the Company's CARDIO inCode-Score® Polygenic Risk Score ("PRS") for coronary heart disease ("CHD"). JACC: Advances, a medical journal which is part of the Journal of the American College of Cardiology (JACC), specifically focuses on the latest research in cardiovascular medicine including new treatments, technologies and scientific discoveries in Cardiology leading to better clinical practices in the medical field.

The peer-reviewed study^1., titled "Joint Consideration of LDL-C and Polygenic Risk for Coronary Heart Disease Risk Assessment", was conducted by researchers at Kaiser Permanente's Department of Research and Department of Cardiology in San Francisco, California, USA.

Study Overview

The Kaiser Permanente study followed over 47,000 individuals of diverse ancestry for 14 years, analysing the relationship between low-density lipoprotein cholesterol (LDL-C) and polygenic risk for coronary heart disease. Participants were assessed for the incidence of CHD events including myocardial infarction (heart attack).

The CARDIO inCode-Score® PRS was used to quantify each participant's inherited risk of CHD based on genetic variation across the genome. The study examined whether the effect of LDL-cholesterol on CHD risk was modified by an individual's underlying genetic risk.

Key Findings

The results demonstrated that genetic risk significantly influences the relationship between LDL-cholesterol and coronary heart disease, with the combination of elevated LDL-C and high PRS conferring substantially greater risk.

·      Individuals with high polygenic risk experienced a 75% increase in CHD risk at LDL-C levels as low as 100 mg/dL (2.6 mmol/L) (Hazard Ratio: 1.75).

·      At LDL-C levels of 130-160 mg/dL (3.4 - 4.1 mmol/L), risk increased more than twofold (HR: 2.1).

·      The combination of a high PRS and LDL-C of 190 mg/dL (4.9 mmol/L) or higher was associated with a greater than 3.5-fold increase in CHD risk, comparable to the risk observed in patients with heterozygous familial hypercholesterolemia (FH), a well-established genetic condition conferring very high cardiovascular risk.

These findings confirm that polygenic risk acts as a powerful modifier of LDL-cholesterol-related CHD risk, supporting its use in clinical decision-making and preventive care.

Clinical and Preventive Implications

This study underscores the critical role that integrating genetic data with clinical assessments can play in revolutionising cardiovascular risk stratification and prevention and guide earlier intervention in at-risk populations.

Individuals with high genetic risk may benefit from more proactive lipid management and lifestyle or therapeutic intervention, even at LDL-C levels traditionally considered low or moderate.

By integrating polygenic risk assessment into existing clinical pathways, healthcare providers can more accurately identify individuals at heightened lifetime risk of CHD and personalise prevention strategies. This can also reduce the incidence of severe cardiovascular events, such as heart attacks and strokes, and potentially mitigate the economic costs associated with long-term heart disease care. This approach can be seen as a significant step toward improving public health outcomes, particularly in addressing the global burden of cardiovascular disease.

Dr. Richard Kovacs, Q.E. and Sally Russell Professor of Cardiology at the Indiana University School of Medicine and Chief Medical Officer of the American College of Cardiology and Past President of the American College of Cardiology said: "These results provide further compelling clinical evidence for the inclusion of polygenic risk scores (PRS) in conjunction with clinical risk for improved risk assessment of CHD. The polygenic risk score is especially important in relation to patients clinically classified at borderline/intermediate risk and younger patients with a family history of CHD. The recent scientific statements and acknowledgment of the value of PRS by the American College of Cardiology and American Heart Association is also welcome." 

1. -  https://share.google/nQwFO73QgGTiRqK45

Notes to Editors

·      Hazard Ratio (HR) refers to the measure of relative risk over time. For example, an HR of 2.0 indicates that an event (such as CHD) is twice as likely to occur in one group compared to another.

·      LDL-cholesterol (LDL-C) is commonly referred to as "bad" cholesterol and is a well-established modifiable risk factor for coronary heart disease.

·      The Journal of the American College of Cardiology (JACC): Advances is a leading peer-reviewed journal publishing high-quality cardiovascular research.

For more information visit www.genincode.com

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