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Post-GWAS multiomic...
Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3
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Panyard, Daniel J. (author)
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Reus, Lianne M. (author)
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Ali, Muhammad (author)
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Liu, Jihua (author)
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Deming, Yuetiva K. (author)
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Lu, Qiongshi (author)
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Kollmorgen, Gwendlyn (author)
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Carboni, Margherita (author)
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Wild, Norbert (author)
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Visser, Pieter J. (author)
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Bertram, Lars (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Gobom, Johan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Western, Dan (author)
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Sung, Yun Ju (author)
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Carlsson, Cynthia M. (author)
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Johnson, Sterling C. (author)
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Asthana, Sanjay (author)
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Cruchaga, Carlos (author)
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Tijms, Betty M. (author)
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Engelman, Corinne D. (author)
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Snyder, Michael P. (author)
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
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https://doi.org/10.1...
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Abstract
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- INTRODUCTION Recent genome-wide association studies (GWAS) have reported a genetic association with Alzheimer's disease (AD) at the TNIP1/GPX3 locus, but the mechanism is unclear. METHODS We used cerebrospinal fluid (CSF) proteomics data to test (n = 137) and replicate (n = 446) the association of glutathione peroxidase 3 (GPX3) with CSF biomarkers (including amyloid and tau) and the GWAS-implicated variants (rs34294852 and rs871269). RESULTS CSF GPX3 levels decreased with amyloid and tau positivity (analysis of variance P = 1.5 x 10(-5)) and higher CSF phosphorylated tau (p-tau) levels (P = 9.28 x 10(-7)). The rs34294852 minor allele was associated with decreased GPX3 (P = 0.041). The replication cohort found associations of GPX3 with amyloid and tau positivity (P = 2.56 x 10(-6)) and CSF p-tau levels (P = 4.38 x 10(-9)). DISCUSSION These results suggest variants in the TNIP1 locus may affect the oxidative stress response in AD via altered GPX3 levels.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Alzheimer's disease
- genomics
- genome-wide association studies
- glutathione peroxidase 3
- proteomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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Panyard, Daniel ...
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Reus, Lianne M.
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Ali, Muhammad
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Liu, Jihua
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Deming, Yuetiva ...
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Lu, Qiongshi
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show more...
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Kollmorgen, Gwen ...
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Carboni, Margher ...
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Wild, Norbert
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Visser, Pieter J ...
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Bertram, Lars
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Gobom, Johan
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Western, Dan
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Sung, Yun Ju
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Carlsson, Cynthi ...
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Johnson, Sterlin ...
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Asthana, Sanjay
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Cruchaga, Carlos
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Tijms, Betty M.
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Engelman, Corinn ...
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Snyder, Michael ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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ALZHEIMERS & DEM ...
- By the university
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University of Gothenburg
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Karolinska Institutet