The paper uses long-read sequencing to uncover structural complexity in Alzheimer's disease GWAS loci, showing that lead SNPs often miss key regulatory variants.

medRxiv · Aug 17, 2026 · PreprintGenetic & Genomic Medicine

The genetic architecture of trabecular bone score and association with fracture: a genome-wide association and meta-analysis

Haojie Lu, Griffin Tibbitts, Gloria Hoi‐Yee Li, Monika Frysz, Christine W. Lary, Katerina Trajanoska, Nilabhra Rohan Das, C.P.G.M. de Groot, Ching‐Lung Cheung, Natasja M. van Schoor, André Gerardus Uitterlinden, Nathalie van der Velde, Jonathan H. Tobias, Fernando Rivadeneira, David M. Evans, , Carolina Medina‐Gómez

This study identifies 33 genetic variants associated with trabecular bone score (TBS) and finds a potential causal link between TBS and fracture risk independent of bone mineral density.

bioRxiv · Oct 1, 2025 · PreprintGenomics

Increased Genetic Protection Against Alzheimer's Disease in Centenarians

Harold T. Bae, Zeyuan Song, Amanat Ali, Takashi Sasaki, Niccoló Tesi, Hannah J. Lords, Anastasia Leshchyk, Yukiko Abe, Nobuyoshi Hirose, Yasumichi Arai, Nir Barzilai, Erica F Weiss, Marc Hulsman, Sven J. van der Lee, Natasja M. van Schoor, , Paola Sebastiani B

This study constructs a polygenic protective score for Alzheimer's disease and finds stronger genetic protection against AD in centenarians compared to non-longevity individuals.

GeroScience · Jul 4, 2025Peer-reviewedGenetics

Cognitively healthy centenarians are characterized by lower frequencies of six disease-associated HLA alleles

Daniel Álvarez Sirvent, Niccoló Tesi, Marc Hulsman, Alex Salazar, Natasja M. van Schoor, Martijn A. Huisman, Yolande A.L. Pijnenburg, Wiesje M. van der Flier, Eva M. M. Strijbis, Bernard M.J. Uitdehaag, Marcel J. T. Reinders, Sven J. van der Lee, Henne H. Holstege

The paper identifies six HLA alleles associated with reduced likelihood of becoming a cognitively healthy centenarian, revealing pleiotropic effects on disease susceptibility and longevity.

medRxiv · Mar 30, 2025 · PreprintGenetic & Genomic Medicine

Genetic Variants that Modulate Alzheimer's Disease Risk Deregulate Protein-Protein Correlations in the Gyrus Temporalis Medius

Gerard A. Bouland, Niccoló Tesi, Meng Zhang, Andrea B. Ganz, Marc Hulsman, Sven J. van der Lee, Marieke Graat, Annemieke J.M. Rozemüller, Martijn A. Huisman, Natasja M. van Schoor, Wiesje M. van der Flier, Jeroen J.M. Hoozemans, August Benjamin Smit, Marcel J. T. Reinders, Henne H. Holstege

The paper identifies genetic variants associated with protein abundance and altered protein-protein correlations in the Gyrus Temporalis Medius in Alzheimer's Disease patients.

medRxiv · Feb 11, 2025 · PreprintGenetic & Genomic Medicine

Fine-mapping reveals four TMEM106B haplotypes associated with neurodegenerative risk and preserved cognition at extreme age

Alex Salazar, Niccoló Tesi, Lydian Knoop, Natasja M. van Schoor, Martijn A. Huisman, Betty Marije Tijms, Everard G.B. Vijverberg, Sven J. van der Lee, Sanduni Wijesekera, Jana Křížová, Mikko Hiltunen, Markus Daμμe, Leonard Petrucelli, Marcel J. T. Reinders, Anke A. Dijkstra, , Henne H. Holstege

medRxiv · Feb 2, 2025 · PreprintGenetic & Genomic Medicine

The effect of Alzheimer's disease-associated genetic variants on longevity

Niccoló Tesi, Marc Hulsman, Sven J. van der Lee, Iris E. Jansen, Najada Stringa, Natasja M. van Schoor, Philip Scheltens, Wiesje M. van der Flier, Martijn A. Huisman, Marcel J. T. Reinders, Henne H. Holstege

This study examines how Alzheimer's disease-associated genetic variants influence longevity by analyzing their effects in centenarians and replicating findings in a parental-longevity GWAS.

Frontiers in Genetics · Dec 21, 2021Peer-reviewedGenetic & Genomic Medicine

Genome Wide Association Metanalysis Of Skull Bone Mineral Density Identifies Loci Relevant For Osteoporosis And Craniosynostosis

Carolina Medina‐Gómez, Benjamin H. Mullin, Alessandra Chesi, Vid Prijatelj, John P. Kemp, Chen Shochat-Carvalho, Katerina Trajanoska, Carol A. Wang, Raimo Joro, Tavia E. Evans, Katharina E. Schraut, Ruifang Li‐Gao, Tarunveer S. Ahluwalia, M. Carola Zillikens, Kun Zhu, , Fernando Rivadeneira

This study identifies 59 genome-wide significant loci for skull bone mineral density, including four novel loci, and links them to osteoporosis and craniofacial developmental defects.

medRxiv · Nov 1, 2021 · PreprintGenetic & Genomic Medicine

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

Garan Jones, Katerina Trajanoska, Adam J. Santanasto, Najada Stringa, Chia‐Ling Kuo, Janice L. Atkins, Joshua Richard Lewis, ThuyVy Duong, Shengjun Hong, Mary Lou Biggs, Jian’an Luan, Chloé Sarnowski, Kathryn L. Lunetta, Toshiko Tanaka, Mary K. Wojczynski, , Luke C. Pilling

This study identifies 15 genetic loci associated with muscle weakness in older adults through a large meta-analysis, revealing new pathways linked to aging and health outcomes.

Nature Communications · Jan 28, 2021Peer-reviewedGenetic & Genomic Medicine

Immune response and endocytosis pathways are associated with the resilience against Alzheimer's Disease

Niccoló Tesi, Sven J. van der Lee, Marc Hulsman, Iris E. Jansen, Najada Stringa, Natasja M. van Schoor, Philip Scheltens, Wiesje M. van der Flier, Martijn A. Huisman, Marcel J. T. Reinders, Henne H. Holstege

The paper identifies immune response and endocytosis pathways as associated with resilience against Alzheimer's Disease using polygenic risk scores across multiple cohorts.

Translational Psychiatry · Sep 29, 2020Peer-reviewedGenetic & Genomic Medicine

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

John A. Lees, Bart Ferwerda, Philip H. C. Kremer, Nicole E. Wheeler, Mercedes Valls Serón, Nicholas J. Croucher, Rebecca A. Gladstone, Hester J. Bootsma, Nynke Y. Rots, Alienke J. Wijmenga‐Monsuur, Elisabeth A. M. Sanders, Krzysztof Trzciński, Anne L. Wyllie, Aeilko Having Zwinderman, Leonard H. van den Berg, , Diederik van de Beek

The paper uses genome-wide association studies to show human and pneumococcal genetic variation influences susceptibility and severity of pneumococcal meningitis.

Nature Communications · May 15, 2019Peer-reviewedGenomics

Centenarian Controls Increase Variant Effect-sizes by an average two-fold in an Extreme Case-Extreme Control Analysis of Alzheimer’s Disease

Niccoló Tesi, Sven J. van der Lee, Marc Hulsman, Iris E. Jansen, Najada Stringa, Natasja M. van Schoor, Hanne E.J. Meijers-Heijboer, Martijn A. Huisman, Philip Scheltens, Marcel J. T. Reinders, Wiesje M. van der Flier, Henne H. Holstege

This study shows that using centenarians as extreme controls increases AD variant effect-sizes by two-fold, enabling replication in small samples.

European Journal of Human Genetics · Sep 26, 2018Peer-reviewedGenetics