What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Cardiometabolic diseases (Type 2 diabetes, obesity, hypertension, coronary artery disease) (n=195780). Intervention: Positive family history and polygenic risk scores (PRS) vs. Negative family history and intermediate/low PRS. Primary outcome: Obesity incidence (associated with positive family history) (HR 2.07, 95% CI 2.02 - 2.12, p=<0.001).

What does this research mean for the field?

Family history (FH) and polygenic risk scores (PRS) enhance risk stratification for cardiometabolic disease, with PRS adding predictive value beyond FH. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

What question did this study set out to answer?

To evaluate how family history and polygenic risk scores affect the risk of cardiometabolic diseases.

February 5, 2026Open Access

Evaluating the impact of family history and polygenic risk scores on cardiometabolic disease risk

Q: What are the key findings of this study?

Positive family history and high polygenic risk scores independently and jointly increased the risk of cardiometabolic diseases, with their combination conferring over a 2.5-fold risk increase.

Q: What does this research mean for the field?

Family history (FH) and polygenic risk scores (PRS) enhance risk stratification for cardiometabolic disease, with PRS adding predictive value beyond FH. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

Q: What question did this study set out to answer?

To evaluate how family history and polygenic risk scores affect the risk of cardiometabolic diseases.

EOEbuka OnyenobiUniversity of Maryland, Baltimore KOKnightess OyiboUniversity of Maryland, Baltimore MZMichael ZhongUniversity of Maryland, Baltimore

Key Result

Positive family history and high polygenic risk scores independently and jointly increased the risk of cardiometabolic diseases, with their combination conferring over a 2.5-fold risk increase.

Key Points

To evaluate how family history and polygenic risk scores affect the risk of cardiometabolic diseases.
Analytical assessment of family history (FH) and polygenic risk scores (PRS)
Comparative analysis of FH and PRS contributions to disease risk
Integration of both measures for improved assessment
Both FH and PRS are associated with cardiometabolic disease risk
PRS offers additional predictive value beyond FH
Comprehensive integration of FH and PRS improves risk stratification

Study Design

Type

Cross-Sectional (n=195,780)

Multicenter

Yes

Structured PICO

Does the integration of family history and polygenic risk scores enhance cardiometabolic disease risk stratification?

Population

Individuals assessed for cardiometabolic disease (CMD) risk

Intervention

Integration of family history (FH) and polygenic risk scores (PRS)

Outcome

Cardiometabolic disease (CMD) risk prediction

Integrating family history and polygenic risk scores provides complementary insights that may enhance cardiometabolic risk stratification and guide precision prevention.

Main Result

Effect estimate: HR 2.07 (95% CI 2.02 - 2.12)

p-value: p=<0.001

Abstract

Both FH and PRS are associated with CMD risk and provide complementary but distinct insights into disease risk. PRS adds predictive value beyond FH and partially mediates its effect. Integration of both measures may enhance risk stratification and guide precision prevention strategies.

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