ArticleGenome medicine2022
A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease.Molecular psychiatry · 2023Pooled it
- A founder population reveals genetic variation with major effect on serious mental illness.medRxiv : the preprint server for health sciences · 2026Article
- Phenotypic diversity of frontotemporal lobar degeneration in two novel GRN variants from Colombia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Multiple-testing corrections in case-control studies using identity-by-descent segments.American journal of human genetics · 2026Article
- Low Frequency of Dementia with Lewy Bodies Diagnosis in a Colombian Memory Clinic.Movement disorders clinical practice · 2026Article
- Genetic contributions to Alzheimer's disease and frontotemporal dementia in admixed Latin American populations.NPJ dementia · 2026Article
- Computational whole-body-exposome models for global precision brain health.Nature communications · 2025Article
- A Japanese familial spastic paraplegia associated with a missense UBQLN2 variant.Journal of human genetics · 2025Article
- Brain banks in Latin America: Infrastructure for diagnosis, research, and scientific equity in Mexico and the Caribbean.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Refining rare disease variant discovery in an isolated Andean community through imputation-enhanced IBD and kinship inference from whole exome sequencing data.Human molecular genetics · 2025Article
- Lewy Body Dementia Research in Latin America: A Scoping Review.Movement disorders clinical practice · 2025Article
- Multiple-testing corrections in case-control studies using identity-by-descent segments.bioRxiv : the preprint server for biology · 2025Article
- Insights into pathophysiology, biomarkers, and therapeutics in tauopathies: Proceedings of the Tau2024 Global Conference.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The impact of rare genetic variants on Alzheimer disease.Nature reviews. Neurology · 2025Review
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Primary lateral sclerosis associated with PSEN1 Pro284Leu variant in a Colombian family: Clinical and neuropathological features.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
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Corrections and comments
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Authors and funding
32 authors at 10 institutions in 4 countries.
Funding
Abstract
backgroundThe Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries.
methodsWe characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes.
resultsWe identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent.
conclusionsColombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.