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Salud Pública

Clayton O Mansel1, Soniya Mishra2, Diego R Mazzotti2

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|December 23, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Las puntuaciones poligénicas (PGS) muestran una mayor asociación con la prevalencia de demencia. Los factores de riesgo modificables, comunes en pacientes con demencia, pueden influir en las evaluaciones de riesgo genómico, lo que requiere un estudio adicional.

Palabras clave:
puntuaciones poligénicasdemenciafactores de riesgo modificablesevaluación de riesgo genómicosalud pública

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Área de la Ciencia:

  • Genómica
  • Neurociencia
  • Salud Pública

Sus antecedentes:

  • Las evaluaciones de riesgo genómico pueden mejorar la atención de la demencia a través de la estratificación y la predicción del tratamiento.
  • Las puntuaciones poligénicas (PGS) evalúan el riesgo genético acumulativo, pero tienen una menor precisión en las ascendencias no europeas y en los niveles socioeconómicos bajos.
  • Las interacciones gen-ambiente, que involucran factores de riesgo modificables, pueden influir en la precisión de las PGS.

Objetivo del estudio:

  • Calibrar las puntuaciones poligénicas (PGS) para la evaluación del riesgo de demencia.
  • Investigar la interacción entre PGS y 12 factores de riesgo modificables para la demencia.
  • Probar la hipótesis de que un PGS alto amplifica el riesgo de demencia en individuos con factores de riesgo cardiometabólico.

Principales métodos:

  • Se utilizaron registros de salud electrónicos del programa All of Us Research para identificar casos de demencia.
  • Se generaron puntuaciones poligénicas (PGS) utilizando secuenciación del genoma completo (WGS) para un subconjunto de casos y controles.
  • Se empleó regresión logística ajustada por covariables para probar la asociación entre PGS y diagnóstico de demencia.

Principales resultados:

  • De 245.366 participantes, 3.222 tenían demencia; la hipertensión (87%) y la depresión (63%) fueron las más prevalentes.
  • Un aumento de 1 desviación estándar en PGS se asoció con un mayor diagnóstico de demencia (OR: 1,29 [1,05-1,58]).
  • Los datos de WGS incluyeron diversas ascendencias, con 1.491 de ascendencia europea.

Conclusiones:

  • La mayoría de los pacientes con demencia tienen factores de riesgo cardiometabólico coexistentes, lo que podría afectar las evaluaciones de riesgo genómico.
  • Las puntuaciones poligénicas (PGS) más altas están relacionadas con la prevalencia de demencia, lo que ayuda a identificar a las personas en riesgo.
  • La investigación futura explorará las interacciones de PGS con factores de riesgo modificables en el conjunto de datos completo.