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A missense variant in SHARPIN mediates Alzheimer's disease-specific brain damages
DC Field | Value | Language |
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dc.contributor.author | Park, Jun Young | - |
dc.contributor.author | Lee, Dongsoo | - |
dc.contributor.author | Lee, Jang Jae | - |
dc.contributor.author | Gim, Jungsoo | - |
dc.contributor.author | Gunasekaran, Tamil Iniyan | - |
dc.contributor.author | Choi, Kyu Yeong | - |
dc.contributor.author | Kang, Sarang | - |
dc.contributor.author | Do, Ah Ra | - |
dc.contributor.author | Jo, Jinyeon | - |
dc.contributor.author | Park, Juhong | - |
dc.contributor.author | Park, Kyungtaek | - |
dc.contributor.author | Li, Donghe | - |
dc.contributor.author | Lee, Sanghun | - |
dc.contributor.author | Kim, Hoowon | - |
dc.contributor.author | Dhanasingh, Immanuel | - |
dc.contributor.author | Ghosh, Suparna | - |
dc.contributor.author | Keum, Seula | - |
dc.contributor.author | Choi, Jee Hye | - |
dc.contributor.author | Song, Gyun Jee | - |
dc.contributor.author | Sael, Lee | - |
dc.contributor.author | Rhee, Sangmyung | - |
dc.contributor.author | Lovestone, Simon | - |
dc.contributor.author | Kim, Eunae | - |
dc.contributor.author | Moon, Seung Hwan | - |
dc.contributor.author | Kim, Byeong C. | - |
dc.contributor.author | Kim, SangYun | - |
dc.contributor.author | Saykin, Andrew J. | - |
dc.contributor.author | Nho, Kwangsik | - |
dc.contributor.author | Lee, Sung Haeng | - |
dc.contributor.author | Farrer, Lindsay A. | - |
dc.contributor.author | Jun, Gyungah R. | - |
dc.contributor.author | Won, Sungho | - |
dc.contributor.author | Lee, Kun Ho | - |
dc.date.accessioned | 2022-05-23T05:21:19Z | - |
dc.date.available | 2022-05-23T05:21:19Z | - |
dc.date.created | 2021-12-07 | - |
dc.date.issued | 2021-11 | - |
dc.identifier.citation | Translational Psychiatry, Vol.11 No.1, p. 590 | - |
dc.identifier.issn | 2158-3188 | - |
dc.identifier.uri | https://hdl.handle.net/10371/180068 | - |
dc.description.abstract | Established genetic risk factors for Alzheimer's disease (AD) account for only a portion of AD heritability. The aim of this study was to identify novel associations between genetic variants and AD-specific brain atrophy. We conducted genome-wide association studies for brain magnetic resonance imaging measures of hippocampal volume and entorhinal cortical thickness in 2643 Koreans meeting the clinical criteria for AD (n = 209), mild cognitive impairment (n = 1449) or normal cognition (n = 985). A missense variant, rs77359862 (R274W), in the SHANK-associated RH Domain Interactor (SHARPIN) gene was associated with entorhinal cortical thickness (p = 5.0 x 10(-9)) and hippocampal volume (p = 5.1 x 10(-12)). It revealed an increased risk of developing AD in the mediation analyses. This variant was also associated with amyloid-beta accumulation (p = 0.03) and measures of memory (p = 1.0 x 10(-4)) and executive function (p = 0.04). We also found significant association of other SHARPIN variants with hippocampal volume in the Alzheimer's Disease Neuroimaging Initiative (rs3417062, p = 4.1 x 10(-6)) and AddNeuroMed (rs138412600, p = 5.9 x 10(-5)) cohorts. Further, molecular dynamics simulations and co-immunoprecipitation indicated that the variant significantly reduced the binding of linear ubiquitination assembly complex proteins, SHPARIN and HOIL-1 Interacting Protein (HOIP), altering the downstream NF-kappa B signaling pathway. These findings suggest that SHARPIN plays an important role in the pathogenesis of AD. | - |
dc.language | 영어 | - |
dc.publisher | Nature Publishing Group | - |
dc.title | A missense variant in SHARPIN mediates Alzheimer's disease-specific brain damages | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/s41398-021-01680-5 | - |
dc.citation.journaltitle | Translational Psychiatry | - |
dc.identifier.wosid | 000719319300001 | - |
dc.identifier.scopusid | 2-s2.0-85119379888 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 590 | - |
dc.citation.volume | 11 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Won, Sungho | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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