Predicting Neurodegenerative Diseases: Unveiling the Interplay of Genetics and Social Determinants

Abstract Background Predicting Alzheimer's disease (AD) and frontotemporal dementia (FTD) using polygenic risk scores (PRS) for late‐onset forms holds promise, but its accuracy might be influenced by social determinants of health (SDOH). This study explores how considering SDOH alongside genes can improve prediction, focusing on potential differences for each disease. Methods Employing logistic regression in 677 individuals (287 AD, 102 FTD, and 288 controls) aged 40‐80 from the ReDLat study across six Latin American countries, we investigated the potential for SDOH to modify the association between PRS and susceptibility to AD and FTD. Analyses were adjusted for a probabilistic score derived from models comparing disease groups to controls with SDOH data (education, occupation, economic stability, healthcare access and quality, and social context) and APOE ε4 carrier status to account for confounding effects. Results Although univariate association tests revealed robust links between PRS and both diseases, adjusted models presented a nuanced picture. In AD, the SDOH score and APOE ε4 carrier status significantly attenuated the PRS effect (p=0.14), suggesting these factors modify genetic risk. In FTD, however, SDOH did not influence the PRS contribution. These findings highlight the potentially distinct roles of social factors in different neurodegenerative pathways. Conclusion The significant modification of PRS effects in AD by SDOH and APOE ε4 underscores the need for comprehensive approaches in future research and interventions in Latin America. Conversely, the unaltered PRS contribution in FTD emphasizes distinct intricacies in gene‐environment interactions. These findings necessitate considering both realms in future efforts, paving the way for targeted strategies in AD and FTD prevention and treatment.

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Publication Details

Journal
Alzheimer s & Dementia
Published
2024-12-01
DOI
https://doi.org/10.1002/alz.089721
Primary Topic
Health, Environment, Cognitive Aging
Type
article
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article

Predicting Neurodegenerative Diseases: Unveiling the Interplay of Genetics and Social Determinants

Nilton Custodio, Teresita Ramos Franco, Stefanie Danielle Piña‐Escudero, Leonel Tadao Takada et al.
Alzheimer s & Dementia
Health, Environment, Cognitive Aging
article

Predicting Neurodegenerative Diseases: Unveiling the Interplay of Genetics and Social Determinants

Nilton Custodio, Teresita Ramos Franco, Stefanie Danielle Piña‐Escudero, Leonel Tadao Takada, María Beatriz Bistué Millón, Pablo Reyes, Agustín M. Ibáñez, Maria Eugenia Godoy, Kenneth S. Kosik, Jared W. Taylor, María Isabel Behrens, Joaquín Migeot, Mike A. Nalls, Rosa Montesinos, Bruce L. Miller, Marcelo Adrián Maito, J. Nicholas Cochran, Jennifer S. Yokoyama, Martín A. Bruno, Andrea Slachevsky, Nancy Gélvez, Hernán Hernandez, Juliana Acosta‐Uribe, Bárbara Bruna, Shireen Javandel, Diana Matallana, Caroline B. Pantazis, Dan Vitale, José Alberto Ávila‐Funes, Luis Ignacio Brusco, Dafne Estefania Durón, Elisa de Paula, Andrew Singleton, França Resende, Daniela P. Ponce
article en

Abstract

Abstract Background Predicting Alzheimer's disease (AD) and frontotemporal dementia (FTD) using polygenic risk scores (PRS) for late‐onset forms holds promise, but its accuracy might be influenced by social determinants of health (SDOH). This study explores how considering SDOH alongside genes can improve prediction, focusing on potential differences for each disease. Methods Employing logistic regression in 677 individuals (287 AD, 102 FTD, and 288 controls) aged 40‐80 from the ReDLat study across six Latin American countries, we investigated the potential for SDOH to modify the association between PRS and susceptibility to AD and FTD. Analyses were adjusted for a probabilistic score derived from models comparing disease groups to controls with SDOH data (education, occupation, economic stability, healthcare access and quality, and social context) and APOE ε4 carrier status to account for confounding effects. Results Although univariate association tests revealed robust links between PRS and both diseases, adjusted models presented a nuanced picture. In AD, the SDOH score and APOE ε4 carrier status significantly attenuated the PRS effect (p=0.14), suggesting these factors modify genetic risk. In FTD, however, SDOH did not influence the PRS contribution. These findings highlight the potentially distinct roles of social factors in different neurodegenerative pathways. Conclusion The significant modification of PRS effects in AD by SDOH and APOE ε4 underscores the need for comprehensive approaches in future research and interventions in Latin America. Conversely, the unaltered PRS contribution in FTD emphasizes distinct intricacies in gene‐environment interactions. These findings necessitate considering both realms in future efforts, paving the way for targeted strategies in AD and FTD prevention and treatment.

Alzheimer s & DementiaVol. 20(S2)
National Institutes of Health (US), Universidad del Desarrollo (CL), Consejo Nacional de Investigaciones Científicas y Técnicas (AR), University of California, Santa Barbara (US), University of California, San Francisco (US), Trinity College Dublin (IE), Adolfo Ibáñez University (CL), Pontificia Universidad Javeriana (CO), Universidad de Buenos Aires (AR), Clínica Alemana (CL), Universidad de Antioquia (CO), University of San Andrés (AR), Data Tecnica International (United States) (US), Centro Científico Tecnológico - San Juan (AR), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX), Hospital del Salvador (CL), University Memory and Aging Center (US), Faculdade de Ciências Médicas de Minas Gerais (BR), National Institute of Neurological Disorders and Stroke (US), Universidad Católica de Cuyo (AR), Hospital Clínico de la Universidad de Chile (CL), Fundación Santa Fe de Bogotá (CO), Institute of Peruvian Studies (PE), National Institute on Aging (US), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), HudsonAlpha Institute for Biotechnology (US), Center for Climate and Resilience Research (CL), Hospital Universitario San Ignacio (CO), Global Brain Health Institute (US), McGill University (CA), University of Chile (CL)
Openalex Percentile: Top 65%
Health, Environment, Cognitive Aging
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