The genetic overlap between Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease

Douglas P. Wightman, Jeanne E. Savage, Elleke Tissink, Cato Romero, Iris E. Jansen, Danielle Posthuma

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)


Neurodegenerative diseases are a group of disorders characterized by neuronal cell death causing a variety of physical and mental problems. While these disorders can be characterized by their phenotypic presentation within the nervous system, their aetiologies differ to varying degrees. The majority of previous genetic evidence for overlap between neurodegenerative diseases has been pairwise. In this study, we aimed to identify overlap between the 4 investigated neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease) at the variant, gene, genomic locus, gene-set, cell, or tissue level, with specific interest in overlap between 3 or more diseases. Using local genetic correlation, we found 2 loci (TMEM175 and HLA) that were shared across 3 disorders. We also highlighted genes, genomic loci, gene sets, cell types, and tissue types which may be important to 2 or more disorders by analyzing the association of variants with a common factor estimated from the 4 disorders. Our study successfully highlighted genetic loci and tissues associated with 2 or more neurodegenerative diseases.
Original languageEnglish
Pages (from-to)99-112
Number of pages14
JournalNeurobiology of aging
Early online date2023
Publication statusPublished - Jul 2023


  • Alzheimer's disease
  • Amyotrophic lateral sclerosis
  • Genetic overlap
  • Global genetic correlation
  • Lewy body dementia
  • Local genetic correlation
  • Parkinson's disease

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