Non-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women.
dementia
sex-specific
stroke
whole-genome sequence
women
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
02
03
2020
revised:
17
07
2020
accepted:
03
08
2020
pubmed:
24
9
2020
medline:
16
11
2021
entrez:
23
9
2020
Statut:
ppublish
Résumé
Recent studies suggest that both sex-specific genetic risk factors and those shared between dementia and stroke are involved in dementia pathogenesis. 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. 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. 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.
Identifiants
pubmed: 32966694
doi: 10.1002/alz.12181
pmc: PMC7920533
mid: NIHMS1668912
doi:
Substances chimiques
FZD3 protein, human
0
Frizzled Receptors
0
MYH11 protein, human
0
Nerve Tissue Proteins
0
Receptors, Cell Surface
0
SorCS3 protein, human
0
Myosin Heavy Chains
EC 3.6.4.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
215-225Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600002C
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030146
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG049638
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS080820
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117626
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017216
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018023
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059737
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046152
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600018C
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600003C
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032990
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500014C
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600001C
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003949
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025711
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG036836
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Informations de copyright
© 2020 the Alzheimer's Association.
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