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> Keene C. Dirk >
Sex-specific geneti...
Sex-specific genetic predictors of Alzheimer’s disease biomarkers
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- Deming, Yuetiva (author)
- Washington University in St. Louis
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- Dumitrescu, Logan (author)
- Vanderbilt University
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- Barnes, Lisa L. (author)
- Rush University Medical Center Chicago
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- Thambisetty, Madhav (author)
- National Institute on Aging, United States
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- Kunkle, Brian (author)
- Case Western Reserve University
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- Gifford, Katherine A. (author)
- Vanderbilt University
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- Bush, William S. (author)
- Case Western Reserve University
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Chibnik, Lori B. (author)
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- Mukherjee, Shubhabrata (author)
- University of Washington
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- de Jager, Philip L. (author)
- Broad Institute,Columbia University
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- Kukull, Walter (author)
- University of Washington
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Huentelman, Matt (author)
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- Crane, Paul K. (author)
- University of Washington
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- Resnick, Susan M. (author)
- National Institute on Aging, United States
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- Keene, C. Dirk (author)
- University of Washington
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- Montine, Thomas J. (author)
- Stanford University School of Medicine
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Schellenberg, Gerard (author)
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- Haines, Jonathan L. (author)
- Case Western Reserve University
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- Zetterberg, Henrik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Larson, Eric B. (author)
- University of Washington,Kaiser Permanente Research Institute
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Johnson, Sterling C. (author)
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- Albert, Marilyn (author)
- Johns Hopkins University School of Medicine
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- Moghekar, Abhay (author)
- Johns Hopkins University School of Medicine
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- Del Aguila, Jorge L. (author)
- Washington University in St. Louis
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- Fernandez, Maria Victoria (author)
- Washington University in St. Louis
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- Budde, John (author)
- Washington University in St. Louis
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- Hassenstab, Jason (author)
- Washington University in St. Louis
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- Fagan, Anne M. (author)
- Washington University in St. Louis
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- Riemenschneider, Matthias (author)
- Saarland University
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- Petersen, Ronald C. (author)
- Mayo Clinic Minnesota
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- Minthon, Lennart (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Chao, Michael J. (author)
- Icahn School of Medicine at Mount Sinai
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- van Deerlin, Vivianna M. (author)
- University of Pennsylvania
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- Lee, Virginia M.Y. (author)
- University of Pennsylvania
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- Shaw, Leslie M. (author)
- University of Pennsylvania
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- Trojanowski, John Q. (author)
- University of Pennsylvania
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- Peskind, Elaine R. (author)
- University of Washington
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- Li, Gail (author)
- University of Washington,VA Puget Sound Health Care System
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- Davis, Lea K. (author)
- Vanderbilt University
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- Sealock, Julia M. (author)
- Vanderbilt University
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- Cox, Nancy J. (author)
- Vanderbilt University
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Weiner, Michael W. (author)
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Petersen, Ron (author)
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Aisen, Paul (author)
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Jack, Clifford (author)
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Jagust, William (author)
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Trojanowski, John (author)
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Beckett, Laurel (author)
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Goate, Alison M (author)
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Bennett, David A (author)
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Schneider, Julie A (author)
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Jefferson, Angela L (author)
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Hohman, Timothy J (author)
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Washington University in St Louis Vanderbilt University (creator_code:org_t)
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- 2018-07-02
- 2018
- English.
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 136:6, s. 857-872
- Related links:
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http://dx.doi.org/10...
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https://europepmc.or...
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Abstract
Subject headings
Close
- Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer’s disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = − 0.03, p = 4.25 × 10−8; β = 0.03, p = 3.97 × 10−8) than males (β = − 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10−10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD’s genetic architecture.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer disease
- Amyloid
- APOE
- Cerebrospinal fluid biomarkers
- Neuropathology
- Sex difference
- Tau
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database
- By the author/editor
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Deming, Yuetiva
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Dumitrescu, Loga ...
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Barnes, Lisa L.
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Thambisetty, Mad ...
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Kunkle, Brian
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Gifford, Katheri ...
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show more...
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Bush, William S.
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Chibnik, Lori B.
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Mukherjee, Shubh ...
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de Jager, Philip ...
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Kukull, Walter
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Huentelman, Matt
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Crane, Paul K.
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Resnick, Susan M ...
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Keene, C. Dirk
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Montine, Thomas ...
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Schellenberg, Ge ...
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Haines, Jonathan ...
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Zetterberg, Henr ...
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Blennow, Kaj
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Larson, Eric B.
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Johnson, Sterlin ...
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Albert, Marilyn
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Moghekar, Abhay
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Del Aguila, Jorg ...
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Fernandez, Maria ...
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Budde, John
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Hassenstab, Jaso ...
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Fagan, Anne M.
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Riemenschneider, ...
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Petersen, Ronald ...
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Minthon, Lennart
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Chao, Michael J.
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van Deerlin, Viv ...
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Lee, Virginia M. ...
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Shaw, Leslie M.
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Trojanowski, Joh ...
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Peskind, Elaine ...
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Li, Gail
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Davis, Lea K.
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Sealock, Julia M ...
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Cox, Nancy J.
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Weiner, Michael ...
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Petersen, Ron
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Aisen, Paul
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Jack, Clifford
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Jagust, William
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Trojanowski, Joh ...
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Beckett, Laurel
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Goate, Alison M
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Bennett, David A
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Schneider, Julie ...
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Jefferson, Angel ...
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Hohman, Timothy ...
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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
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Acta Neuropathol ...
- By the university
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Lund University
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University of Gothenburg