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Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias


Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study (GWAS), as well as an analysis of known genetic risk loci for AD dementia, using data from 4,914 brain autopsies. Genome-wide significance was observed for 7 genes and pathologic features of AD and related diseases. Twelve of the 22 genetic risk loci for clinically-defined AD dementia were confirmed in our pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for hallmark pathologic features of AD were strongly positive and linear. Our study discovered new genetic associations with specific pathologic features and aligned known genetic risk for AD dementia with specific pathologic changes in a large brain autopsy study of AD and related dementias.


Vyšlo v časopise: Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004606
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004606

Souhrn

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study (GWAS), as well as an analysis of known genetic risk loci for AD dementia, using data from 4,914 brain autopsies. Genome-wide significance was observed for 7 genes and pathologic features of AD and related diseases. Twelve of the 22 genetic risk loci for clinically-defined AD dementia were confirmed in our pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for hallmark pathologic features of AD were strongly positive and linear. Our study discovered new genetic associations with specific pathologic features and aligned known genetic risk for AD dementia with specific pathologic changes in a large brain autopsy study of AD and related dementias.


Zdroje

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Genetika Reprodukčná medicína

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PLOS Genetics


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