Polygenic scores for longitudinal prediction of incident type 2 diabetes in an ancestrally and medically diverse primary care physician network: a patient cohort study.
Genome Med
; 16(1): 63, 2024 04 26.
Article
en En
| MEDLINE
| ID: mdl-38671457
ABSTRACT
BACKGROUND:
The clinical utility of genetic information for type 2 diabetes (T2D) prediction with polygenic scores (PGS) in ancestrally diverse, real-world US healthcare systems is unclear, especially for those at low clinical phenotypic risk for T2D.METHODS:
We tested the association of PGS with T2D incidence in patients followed within a primary care practice network over 16 years in four hypothetical scenarios that varied by clinical data availability (N = 14,712) (1) age and sex; (2) age, sex, body mass index (BMI), systolic blood pressure, and family history of T2D; (3) all variables in (2) and random glucose; and (4) all variables in (3), HDL, total cholesterol, and triglycerides, combined in a clinical risk score (CRS). To determine whether genetic effects differed by baseline clinical risk, we tested for interaction with the CRS.RESULTS:
PGS was associated with incident T2D in all models. Adjusting for age and sex only, the Hazard Ratio (HR) per PGS standard deviation (SD) was 1.76 (95% CI 1.68, 1.84) and the HR of top 5% of PGS vs interquartile range (IQR) was 2.80 (2.39, 3.28). Adjusting for the CRS, the HR per SD was 1.48 (1.40, 1.57) and HR of the top 5% of PGS vs IQR was 2.09 (1.72, 2.55). Genetic effects differed by baseline clinical risk ((PGS-CRS interaction p = 0.05; CRS below the median HR 1.60 (1.43, 1.79); CRS above the median HR 1.45 (1.35, 1.55)).CONCLUSIONS:
Genetic information can help identify high-risk patients even among those perceived to be low risk in a clinical evaluation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Herencia Multifactorial
/
Diabetes Mellitus Tipo 2
Límite:
Adult
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Aged
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Female
/
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Genome Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido