ArticleAnnals of human genetics2012
Genome-wide association and linkage study in the Amish detects a novel candidate late-onset Alzheimer disease gene.
Article in Annals of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos.Translational psychiatry · 2020Pooled it
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- A longitudinal study of age-related traits and cognitive function: The Collaborative Amish Aging and Memory Project (CAAMP).medRxiv : the preprint server for health sciences · 2026Article
- Single-cell spatial map of cis-regulatory elements for disease-related genes in the macaque cortex.Nature communications · 2026Article
- WDR12 and HIVEP3 are contributors to cognitive preservation in Amish SuperAgers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Evidence for reduced somatic T-cell receptor sequence diversity profiles among Midwestern Amish in an aging cohort study.medRxiv : the preprint server for health sciences · 2026Article
- A Decoy Oligodeoxynucleotides Disturbing Forkhead Box O3 Mediated ctnna2 Transcriptional Repression Prevents Postoperative Neurocognitive Disorder in Mice.CNS neuroscience & therapeutics · 2025Article
- Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer's Disease Etiopathology.Antioxidants (Basel, Switzerland) · 2024Review
- Artificial intelligence and open science in discovery of disease-modifying medicines for Alzheimer's disease.Cell reports. Medicine · 2024Review
- Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.medRxiv : the preprint server for health sciences · 2023Article
- Article
- The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish.HGG advances · 2022Article
- The Big Picture of Neurodegeneration: A Meta Study to Extract the Essential Evidence on Neurodegenerative Diseases in a Network-Based Approach.Frontiers in aging neuroscience · 2022Article
- Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons.ACS omega · 2021Article
- The GGLEAM Study: Understanding Glaucoma in the Ohio Amish.International journal of environmental research and public health · 2021Article
- GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs.Frontiers in molecular biosciences · 2021Article
- Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale.Cells · 2020Article
- Downregulation of LUZP2 Is Correlated with Poor Prognosis of Low-Grade Glioma.BioMed research international · 2020Article
- Analysis of Association of Genetic Markers in the LUZP2 and FBXO40 Genes with the Normal Variability in Cognitive Performance in the Elderly.International journal of Alzheimer's disease · 2018Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
To identify novel late-onset Alzheimer disease (LOAD) risk genes, we have analysed Amish populations of Ohio and Indiana. We performed genome-wide SNP linkage and association studies on 798 individuals (109 with LOAD). We tested association using the Modified Quasi-Likelihood Score test and also performed two-point and multipoint linkage analyses. We found that LOAD was significantly associated with APOE (P= 9.0 × 10-6) in all our ascertainment regions except for the Adams County, Indiana, community (P= 0.55). Genome-wide, the most strongly associated SNP was rs12361953 (P= 7.92 × 10-7). A very strong, genome-wide significant multipoint peak [recessive heterogeneity multipoint LOD (HLOD) = 6.14, dominant HLOD = 6.05] was detected on 2p12. Three additional loci with multipoint HLOD scores >3 were detected on 3q26, 9q31 and 18p11. Converging linkage and association results, the most significantly associated SNP under the 2p12 peak was at rs2974151 (P= 1.29 × 10-4). This SNP is located in CTNNA2, which encodes catenin alpha 2, a neuronal-specific catenin known to have function in the developing brain. These results identify CTNNA2 as a novel candidate LOAD gene, and implicate three other regions of the genome as novel LOAD loci. These results underscore the utility of using family-based linkage and association analyses in isolated populations to identify novel loci for traits with complex genetic architecture.
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Registered trials
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.