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Non‐coding variants in MYH11 , FZD3 , and SORCS3 are associated with dementia in women
Author(s) -
Blue Elizabeth E.,
Thornton Timothy A.,
Kooperberg Charles,
Liu Simin,
WactawskiWende Jean,
Manson JoAnn,
Kuller Lew,
Hayden Kathleen,
Reiner Alexander P.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12181
Subject(s) - dementia , genome wide association study , disease , context (archaeology) , locus (genetics) , vascular dementia , genetic association , genetics , gene , medicine , bioinformatics , biology , single nucleotide polymorphism , genotype , paleontology
Recent studies suggest that both sex‐specific genetic risk factors and those shared between dementia and stroke are involved in dementia pathogenesis. Methods We performed both single‐variant and gene‐based genome‐wide association studies of >11,000 whole genome sequences from the Women's Health Initiative cohort to discover loci associated with dementia, with adjustment for age, ethnicity, stroke, and venous thromboembolism status. Evidence for prior evidence of association and differential gene expression in dementia‐related tissues and samples was gathered for each locus. Results Our multiethnic studies identified significant associations between variants within APOE , MYH11 , FZD3 , SORCS3 , and GOLGA8B and risk of dementia. Ten genes implicated by these loci, including MYH11 , FZD3 , SORCS3 , and GOLGA8B , were differentially expressed in the context of Alzheimer's disease. Discussion Our association of MYH11 , FZD3 , SORCS3 , and GOLGA8B with dementia is supported by independent functional studies in human subjects, model systems, and associations with shared risk factors for stroke and dementia.