You are here

Non-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women.

TitleNon-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women.
Publication TypeJournal Article
Year of Publication2021
AuthorsBlue EE, Thornton TA, Kooperberg C, Liu S, Wactawski-Wende J, Manson JA, Kuller L, Hayden K, Reiner AP
JournalAlzheimers Dement
Volume17
Issue2
Pagination215-225
Date Published2021 02
ISSN1552-5279
KeywordsAlzheimer Disease, Cohort Studies, Female, Frizzled Receptors, Genome-Wide Association Study, Humans, Middle Aged, Myosin Heavy Chains, Nerve Tissue Proteins, Receptors, Cell Surface, Risk Factors
Abstract

INTRODUCTION: 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.

DOI10.1002/alz.12181
Pubmed Linkhttps://www.ncbi.nlm.nih.gov/pubmed/32966694?dopt=Abstract
page_expoExternal
Alternate JournalAlzheimers Dement
PubMed ID32966694
PubMed Central IDPMC7920533
Grant ListR01 HL120393 / HL / NHLBI NIH HHS / United States
HHSN268201600002C / HL / NHLBI NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01 NS080820 / NS / NINDS NIH HHS / United States
HHSN268201600004C / HL / NHLBI NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
P01 AG017216 / AG / NIA NIH HHS / United States
R01 AG018023 / AG / NIA NIH HHS / United States
R01 AG059737 / AG / NIA NIH HHS / United States
U01 AG046152 / AG / NIA NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
HHSN268201600018C / HL / NHLBI NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
HHSN268201600003C / HL / NHLBI NIH HHS / United States
R01 AG032990 / AG / NIA NIH HHS / United States
HHSN268201500014C / HL / NHLBI NIH HHS / United States
U01 AG046139 / AG / NIA NIH HHS / United States
HHSN268201600001C / HL / NHLBI NIH HHS / United States
P01 AG003949 / AG / NIA NIH HHS / United States
U24 NS072026 / NS / NINDS NIH HHS / United States
P30 AG019610 / AG / NIA NIH HHS / United States
P50 AG025711 / AG / NIA NIH HHS / United States
U01 AG006786 / AG / NIA NIH HHS / United States
R01 AG036836 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States

Theme by Danetsoft and Danang Probo Sayekti inspired by Maksimer