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Sex differences in ...
Sex differences in the genetic predictors of Alzheimer's pathology
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Dumitrescu, L. (author)
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Barnes, L. L. (author)
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Thambisetty, M. (author)
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Beecham, G. (author)
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Kunkle, B. (author)
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Bush, W. S. (author)
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Gifford, K. A. (author)
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Chibnik, L. B. (author)
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Mukherjee, S. (author)
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De Jager, P. L. (author)
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Kukull, W. (author)
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Crane, P. K. (author)
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Resnick, S. M. (author)
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Keene, C. D. (author)
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Montine, T. J. (author)
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Schellenberg, G. D. (author)
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Deming, Y. (author)
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Chao, M. J. (author)
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Huentelman, M. (author)
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Martin, E. R. (author)
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Hamilton-Nelson, K. (author)
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Shaw, L. M. (author)
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Trojanowski, J. Q. (author)
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Peskind, E. R. (author)
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Cruchaga, C. (author)
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Pericak-Vance, M. A. (author)
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Goate, A. M. (author)
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Cox, N. J. (author)
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Haines, J. L. (author)
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- Zetterberg, Henrik, 1973 (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, 1958 (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, E. B. (author)
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Johnson, S. C. (author)
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Albert, M. (author)
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Bennett, D. A. (author)
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Schneider, J. A. (author)
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Jefferson, A. L. (author)
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Hohman, T. J. (author)
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(creator_code:org_t)
- 2019-07-20
- 2019
- English.
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 142, s. 2581-2589
- Related links:
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https://academic.oup...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Autopsy measures of Alzheimer's disease neuropathology have been leveraged as endophenotypes in previous genome-wide association studies (GWAS). However, despite evidence of sex differences in Alzheimer's disease risk, sex-stratified models have not been incorporated into previous GWAS analyses. We looked for sex-specific genetic associations with Alzheimer's disease endophenotypes from six brain bank data repositories. The pooled dataset included 2701 males and 3275 females, the majority of whom were diagnosed with Alzheimer's disease at autopsy (70%). Sex-stratified GWAS were performed within each dataset and then meta-analysed. Loci that reached genome-wide significance (P < 5 x 10(-8)) in stratified models were further assessed for sex interactions. Additional analyses were performed in independent datasets leveraging cognitive, neuroimaging and CSF endophenotypes, along with age-at-onset data. Outside of the APOE region, one locus on chromosome 7 (rs34331204) showed a sex-specific association with neurofibrillary tangles among males (P = 2.5 x 10(-8)) but not females (P = 0.85, sex-interaction P = 2.9 x 10(-4)). In follow-up analyses, rs34331204 was also associated with hippocampal volume, executive function, and age-at-onset only among males. These results implicate a novel locus that confers male-specific protection from tau pathology and highlight the value of assessing genetic associations in a sex-specific manner.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Brain
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To the university's database
- By the author/editor
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Dumitrescu, L.
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Barnes, L. L.
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Thambisetty, M.
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Beecham, G.
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Kunkle, B.
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Bush, W. S.
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show more...
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Gifford, K. A.
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Chibnik, L. B.
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Mukherjee, S.
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De Jager, P. L.
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Kukull, W.
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Crane, P. K.
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Resnick, S. M.
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Keene, C. D.
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Montine, T. J.
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Schellenberg, G. ...
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Deming, Y.
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Chao, M. J.
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Huentelman, M.
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Martin, E. R.
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Hamilton-Nelson, ...
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Shaw, L. M.
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Trojanowski, J. ...
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Peskind, E. R.
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Cruchaga, C.
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Pericak-Vance, M ...
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Goate, A. M.
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Cox, N. J.
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Haines, J. L.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Larson, E. B.
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Johnson, S. C.
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Albert, M.
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Bennett, D. A.
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Schneider, J. A.
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Jefferson, A. L.
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Hohman, T. J.
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show less...
- About the subject
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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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Brain
- By the university
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University of Gothenburg