ArticleAnnals of neurology2015
Rare coding mutations identified by sequencing of Alzheimer disease genome-wide association studies loci.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Genetic and environmental risk factors for dementia in African adults: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias.medRxiv : the preprint server for health sciences · 2026Article
- Multi-ancestry exome-wide study identifies variants associated with Alzheimer's disease protection.Journal of Alzheimer's disease : JAD · 2026Article
- Circulating pTau181 and Genomic Background in Dogs: A Pilot Study on Neurobiological Aging.Veterinary medicine international · 2026Article
- Amyloid-Related Imaging Abnormality (ARIA) Beyond the APOE-ε4 Allele.Chronic diseases and translational medicine · 2025Review
- Alzheimer's genetic risk factor Bin1 controls synapse vesicle exo-endocytosis in inhibitory synapses.Cell reports · 2025Article
- Genome-wide association studies of Alzheimer's disease and related disorders stratified by sex, onset age, and Apolipoprotein E genotype reveal novel risk loci in African Americans.Alzheimer's research & therapy · 2025Article
- CD2AP at the junction of nephropathy and Alzheimer's disease.Molecular neurodegeneration · 2025Review
- A New Molecular Mechanism for the Late-Onset Alzheimer's Disease Risk Gene CD2AP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The impact of rare genetic variants on Alzheimer disease.Nature reviews. Neurology · 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
- The Alzheimer's Disease Risk Gene CD2AP Functions in Dendritic Spines by Remodeling F-Actin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Identifying Oncogenic Missense Single Nucleotide Polymorphisms in Human SAT1 Gene Using Computational Algorithms and Molecular Dynamics Tools.Cancer reports (Hoboken, N.J.) · 2024Article
- The Abca7Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The ABC's of Alzheimer risk gene ABCA7.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- BIN1Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Alzheimer's disease and Alzheimer's disease-related dementias in Hispanics: Identifying influential factors and supporting caregivers.Ageing research reviews · 2024Review
- Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 7 institutions in 6 countries.
Funding
Abstract
objectiveTo detect rare coding variants underlying loci detected by genome-wide association studies (GWAS) of late onset Alzheimer disease (LOAD).
methodsWe conducted targeted sequencing of ABCA7, BIN1, CD2AP, CLU, CR1, EPHA1, MS4A4A/MS4A6A, and PICALM in 3 independent LOAD cohorts: 176 patients from 124 Caribbean Hispanics families, 120 patients and 33 unaffected individuals from the 129 National Institute on Aging LOAD Family Study; and 263 unrelated Canadian individuals of European ancestry (210 sporadic patients and 53 controls). Rare coding variants found in at least 2 data sets were genotyped in independent groups of ancestry-matched controls. Additionally, the Exome Aggregation Consortium was used as a reference data set for population-based allele frequencies.
resultsOverall we detected a statistically significant 3.1-fold enrichment of the nonsynonymous mutations in the Caucasian LOAD cases compared with controls (p = 0.002) and no difference in synonymous variants. A stop-gain mutation in ABCA7 (E1679X) and missense mutation in CD2AP (K633R) were highly significant in Caucasian LOAD cases, and mutations in EPHA1 (P460L) and BIN1 (K358R) were significant in Caribbean Hispanic families with LOAD. The EPHA1 variant segregated completely in an extended Caribbean Hispanic family and was also nominally significant in the Caucasians. Additionally, BIN1 (K358R) segregated in 2 of the 6 Caribbean Hispanic families where the mutations were discovered.
interpretationTargeted sequencing of confirmed GWAS loci revealed an excess burden of deleterious coding mutations in LOAD, with the greatest burden observed in ABCA7 and BIN1. Identifying coding variants in LOAD will facilitate the creation of tractable models for investigation of disease-related mechanisms and potential therapies.
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