Landscape of copy number variants in Spanish people with dementia

Recent studies suggest that copy number variants (CNVs) may contribute to the missing heritability of complex diseases such as Alzheimer's disease (AD) and related dementias (ADRD). We performed a CNV analysis using genotyping data (Axiom 815 K Spanish biobank array) from the GR@ACE/DEGESCO dementia dataset (n = 20,067) of the Spanish population. Applying PennCNV and extensive quality control, 8275 controls and 7818 dementia cases were selected for gene-level case/control associations. We identified 43,833 CNVs with deletions (47%) and duplications (53%). No genome-wide significant associations were found, but nominal associations were observed in PKP3-SIGIRR and FBRSL1 loci. CNVs in 2970 genes were exclusive to dementia cases and enriched in vascular-related pathways. Notable findings included 14q11.2 duplication and VPS13B deletions in ADRD cases, the latter confirmed by optical genome mapping. Our findings suggest potential novel genes associated with ADRD in the Spanish population. However, the limited resolution of array-based technologies in detecting CNVs warrants further investigation.

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Journal
npj Genomic Medicine
Published
2026-06-30
DOI
https://doi.org/10.1038/s41525-026-00589-6
Primary Topic
Genomic variations and chromosomal abnormalities
Type
article
Field-Weighted Citation Impact
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article

Landscape of copy number variants in Spanish people with dementia

Miquel Baquero, Pilar Cañabate, Luís Miguel Real, Astrid Adarmes‐Gómez et al.
npj Genomic Medicine
Genomic variations and chromosomal abnormalities
article

Landscape of copy number variants in Spanish people with dementia

Miquel Baquero, Pilar Cañabate, Luís Miguel Real, Astrid Adarmes‐Gómez, Gemma Ortega, Juan A. Pineda, Marta Ibarria, Inés Quintela, Laura Montrreal, Sílvia Preckler, Clàudia Olivé, Núria Lleonart, Susanna Seguer, María Capdevila-Bayo, Alba Pérez‐Cordón, Dolores Buiza‐Rueda, Olalla Maroñas, Montserrat Alegret, Xavier Morató, Raquel Huerto Vilas, Carmen Martínez Rodríguez, Irene Rosas Allende, Ana Pancho, Carmen Lage, A. Gailhajenet, Juan Pablo Tartari, Ana Belén Pastor, María Teresa Martínez, Josep Blázquez-Folch, Ana Espinosa, Mariola Moreno, María Bernal Sánchez‐Arjona, Marina Guitart, Asunción Lafuente, Miquel Aguilar, Calero, E. Pelejà, Silvia Mendoza, Nathalia Muñoz, Núria Aguilera, Mar Buendía, Elvira Martín, Susana Diego, Federico Casales, Paula Bayón-Buján, Berta Calm, Sergi Valero, Ángela Sanabria, Sebastian García-Madrona, Maria Teresa Martinez-Larrad, Arturo Corbaton-Anchuelo, Emilio Franco-Macias, Ignacio Alvarez, Monica Diez-Fairen, Ana Frank-García, Natali Bein, Angel Martín-Montes, Maria Victoria Fernández, Jose Luis Royo, DEGESCO, Juan Macías, Alberto Rábano, Pablo García-González, Amanda Cano, Ángel Carracedo, Teodoro del Ser, Oscar Sotolongo-Grau, Itziar de Rojas, A. Corbatón-Anchuelo, Álvaro Muñoz-Morales, Mercè Boada, Andrea Miguel, José Nelet Rodríguez, Manuel Menéndez-González, María Dolores Alonso, Daniel Alcolea, Maria Eugenia Sáez, GR@ACE, Anaïs Corma-Gómez, Raquel Puerta, Luís Tárraga, Maitée Rosende-Roca, Liliana Vargas, Marta Marquié, Carmen Antúnez, Agustín Ruiz, Alfonso Arias Pastor
article en

Abstract

Recent studies suggest that copy number variants (CNVs) may contribute to the missing heritability of complex diseases such as Alzheimer's disease (AD) and related dementias (ADRD). We performed a CNV analysis using genotyping data (Axiom 815 K Spanish biobank array) from the GR@ACE/DEGESCO dementia dataset (n = 20,067) of the Spanish population. Applying PennCNV and extensive quality control, 8275 controls and 7818 dementia cases were selected for gene-level case/control associations. We identified 43,833 CNVs with deletions (47%) and duplications (53%). No genome-wide significant associations were found, but nominal associations were observed in PKP3-SIGIRR and FBRSL1 loci. CNVs in 2970 genes were exclusive to dementia cases and enriched in vascular-related pathways. Notable findings included 14q11.2 duplication and VPS13B deletions in ADRD cases, the latter confirmed by optical genome mapping. Our findings suggest potential novel genes associated with ADRD in the Spanish population. However, the limited resolution of array-based technologies in detecting CNVs warrants further investigation.

npj Genomic Medicine
Universitat Autònoma de Barcelona (ES), Universidad de Cantabria (ES), Universidad de Oviedo (ES), The University of Texas at San Antonio Health Science Center (US), University of Luxembourg (LU), Universidade de Santiago de Compostela (ES), Hospital Universitario La Paz (ES), Instituto de Salud Carlos III (ES), Hospital de Sant Pau (ES), Hospital Clínico San Carlos (ES), Hospital Universitari i Politècnic La Fe (ES), Universitat Internacional de Catalunya (ES), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Instituto de Neurociencias (ES), Hospital Universitari de Santa Maria (ES), Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (ES), Hospital Clínico Universitario de Valencia (ES), University Hospital Mútua de Terrassa (ES), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES), Marqués de Valdecilla University Hospital (ES), Hospital La Paz Institute for Health Research (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Centro Andaluz de Biología del Desarrollo (ES), Center for Research in Molecular Medicine and Chronic Diseases (ES), Institute for Neurodegenerative Disorders (US), Instituto de Investigación Marqués de Valdecilla (ES), Fundación Pública Galega de Medicina Xenómica (ES), Fundació ACE (ES), Instituto Ramón y Cajal de Investigación Sanitaria (ES), Mútua Terrassa (ES), Instituto de Biomedicina de Sevilla (ES), Instituto de Investigación Biomédica de Lleida (ES), Hospital Universitario Central de Asturias (ES), Hospital Universitario de Valme (ES), Hospital Universitario De Cabueñes (ES), Unidad Funcional de Investigación de Enfermedades Crónicas (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitario Virgen del Rocío (ES), Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES), Hospital Universitario Ramón y Cajal (ES), Instituto de Investigación Sanitaria La Fe (ES), Instituto de Investigación Sanitaria del Principado de Asturias (ES), Universidad Autónoma de Madrid (ES), Universitat de Barcelona (ES), Universidad de Sevilla (ES), Universidad de Málaga (ES)
University of Texas System, “la Caixa” Foundation, Deutsche Forschungsgemeinschaft, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Grifols, Instituto de Salud Carlos III, Janssen Pharmaceuticals, NextGenerationEU
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Genomic variations and chromosomal abnormalities
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