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Consorcio de Imagenología de Alzheimer

Tavia E Evans1,2,3, Elizabeth Chudleigh2, Patricia Genius2,4,5

  • 1Radboud University Medical Center, Nijmegen, Netherlands.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 23, 2025
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Resumen
Este resumen es generado por máquina.

La inferencia de ascendencia local identificó nuevas variantes de la enfermedad de Alzheimer (EA) pasadas por alto por los métodos tradicionales. Este enfoque mejora el descubrimiento genético para poblaciones diversas y la medicina personalizada en la investigación de la EA.

Palabras clave:
inferencia de ascendencia localenfermedad de Alzheimermedicina personalizadadescubrimiento genéticopoblaciones diversas

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Área de la Ciencia:

  • Genética; Neurociencia; Salud Poblacional

Sus antecedentes:

  • Comprender el papel de la ascendencia genética en la enfermedad de Alzheimer (EA) es crucial para la equidad en salud. Los estudios de asociación del genoma completo (GWAS) a menudo utilizan la ascendencia global, lo que limita la detección de efectos específicos de la ascendencia. La inferencia de ascendencia local (LAI) ofrece un método refinado para identificar dichos efectos.

Objetivo del estudio:

  • Integrar la LAI con el análisis de asociación genética regional en el cromosoma 19. Identificar variantes locales específicas de la ascendencia asociadas con el volumen del hipocampo (HV) y los niveles de amiloide beta 42 (Aβ42) en el líquido cefalorraquídeo (LCR) en la enfermedad de Alzheimer (EA).

Principales métodos:

  • Se utilizó Gnomix para el análisis de ascendencia local (LAI) del cromosoma 19 y Tractor para el GWAS informado por la ascendencia. Se analizaron el volumen del hipocampo (HV) (N=1325) y el amiloide beta 42 en líquido cefalorraquídeo (CSF-Aβ42) (N=282) en la cohorte ALFA. Se ajustaron los datos por edad, sexo, educación, estado de portador de APOE-ε4 y componentes derivados de LAI.

Principales resultados:

  • La inferencia de ascendencia local (LAI) identificó polimorfismos de un solo nucleótido (SNP) únicos asociados con el volumen del hipocampo (HV) y el líquido cefalorraquídeo (LCR) de Aβ42, que los estudios de asociación del genoma completo (GWAS) tradicionales no detectaron. Se encontraron SNP significativos vinculados a ascendencias africanas (HV) y de Asia occidental (Aβ42) en las regiones de EIF3K y ZNF675. La LAI mejoró la resolución de SNP dentro de la región APOE, destacando su relevancia entre ancestros.

Conclusiones:

  • La LAI es esencial para avanzar en la investigación genética de la EA y comprender la variación genética. Los hallazgos respaldan la inclusión de la LAI en futuros estudios de EA para promover la equidad. Este enfoque ayuda en la medicina personalizada y el descubrimiento genético equitativo para la EA.