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Ciencia básica y patogénesis

Razaq O Durodoye1, Timothy H Ciesielski1, Penelope Benchek2

  • 1Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
PubMed
Resumen
Este resumen es generado por máquina.

La raza y la etnia capturan factores de riesgo no genéticos para la enfermedad de Alzheimer de inicio tardío (LOAD). Estos factores, incluidos los impulsores no médicos de la salud, se asocian de forma independiente con el riesgo de LOAD más allá de las contribuciones genéticas.

Palabras clave:
enfermedad de Alzheimer de inicio tardíorazaetniafactores de riesgo no médicos para la saludpredisposición genética

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Área de la Ciencia:

  • Genética y Genómica; Neurociencia; Salud Pública

Sus antecedentes:

  • La raza y la etnia (R/E) se utilizan con frecuencia para estratificar a los participantes en estudios genéticos de la enfermedad de Alzheimer de inicio tardío (LOAD).; Las categorías de R/E ayudan a identificar alelos de riesgo, cuantificar las variaciones del tamaño del efecto y evaluar las diferencias etiológicas entre grupos.; R/E puede actuar como un sustituto de factores de riesgo extrínsecos no medidos, como la experiencia vivida de la raza/etnia y los impulsores no médicos de la salud (NMDH).

Objetivo del estudio:

  • Estimar las contribuciones no genéticas de R/E al riesgo de LOAD.; Ajustar los factores de riesgo genéticos y la ascendencia al evaluar el impacto de R/E.

Principales métodos:

  • Se utilizaron datos genéticos y demográficos de 42.015 participantes del Consorcio de Genética de la Enfermedad de Alzheimer (ADGC) de diversos grupos de R/E.; Se realizó una regresión logística, ajustando por genotipo APOE, edad, sexo y ascendencia genética, para determinar las contribuciones de NMDH capturadas por R/E.; Se empleó la agrupación K-means para identificar grupos genéticamente distintos y se reevaluaron los modelos de regresión utilizando estos clústeres.

Principales resultados:

  • Los participantes de Asia Oriental (EAS), blancos no hispanos (NHW) e hispanos/latinos (HIS) mostraron una probabilidad significativamente mayor de LOAD en comparación con los individuos negros no hispanos (NHB) (ORs: 2,43, 2,07, 2,04, respectivamente).; La agrupación K-means identificó cinco ascendencias genéticas: africana, de Asia Oriental, europea, amerindia y latina genéticamente mixta.; R/E siguió siendo un predictor significativo del riesgo de LOAD incluso después de ajustar por factores genéticos, lo que indica que captura un riesgo más allá de la genética.

Conclusiones:

  • Los factores extrínsecos, específicamente los NMDH capturados a través de R/E, se asocian de forma independiente con el riesgo de LOAD.; Este estudio destaca la importancia de considerar los factores socioambientales en la investigación de la enfermedad de Alzheimer.