ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Alzheimer's disease multi-ancestry genome-wide interaction and stratified study with smoking.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Alzheimer's disease multi-ancestry genome-wide interaction and stratified study with smoking.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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29 authors.
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Abstract
introductionAlzheimer's disease (AD) has genetic and environmental risk factors, including cigarette smoking. Gene-environment interactions may explain AD missing heritability.
methodsLifetime smoking data from 22,032 European ancestry and 3126 African ancestry participants from the Alzheimer's Disease Genetic Consortium and the Framingham Heart Study were used to conduct genome-wide single nucleotide polymorphism (SNP)-by-smoking interaction and smoking-stratified association studies. For top-ranked loci, brain-derived bulk and single nuclei RNA-sequencing were used for differential expression and colocalization analyses.
resultsAmong smokers only, there was a genome-wide significant association in the APAF1/ANKS1B region (rs12368451; odds ratio = 1.19, 95% confidence interval: [1.12, 1.27], p = 3.0 × 10 DISCUSSION: Potentially causal in smokers via eQTL activity, the top SNP may alter expression of ANKS1B, which encodes amyloid beta precursor protein intracellular domain associated-1, known to regulate amyloid beta plaques. HIGHLIGHTS: Among smokers only, a novel chromosome 12 single nucleotide polymorphism (SNP) near ANKS1B was associated with Alzheimer's disease. Evidence came from European and African ancestry cohorts. RNA-sequencing analyses implicated the top SNP as causal via ANKS1B expression in oligodendrocytes. A genome-wide African ancestry-specific significant SNP-smoking interaction was observed on chromosome 6 in SLC22A23.
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