New Results
Polygenic hazard scores in preclinical Alzheimer’s disease
View ORCID ProfileChin Hong Tan, Leo P. Sugrue, Iris J. Broce, Elizabeth Tong, Jacinth J. X. Tan, Christopher P. Hess, William P. Dillon, Luke W. Bonham, Jennifer S. Yokoyama, Gil D. Rabinovici, Howard J. Rosen, Bruce L. Miller, Bradley T. Hyman, Gerard D. Schellenberg, Lilah M. Besser, Walter A. Kukull, Celeste M. Karch, James B. Brewer, Karolina Kauppi, Linda K. McEvoy, Ole A. Andreassen, Anders M. Dale, Chun Chieh Fan, Rahul S. Desikan
doi: https://doi.org/10.1101/156331
Chin Hong Tan
1Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States of America
PhDLeo P. Sugrue
1Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States of America
MD, PhDIris J. Broce
1Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States of America
PhDElizabeth Tong
1Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States of America
MDJacinth J. X. Tan
2Center for Health and Community, University of California, San Francisco, San Francisco, California, United States of America
PhDChristopher P. Hess
1Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States of America
MD, PhDWilliam P. Dillon
1Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States of America
MDLuke W. Bonham
3Department of Neurology, University of California, San Francisco, San Francisco, California, United States of America
BSJennifer S. Yokoyama
3Department of Neurology, University of California, San Francisco, San Francisco, California, United States of America
PhDGil D. Rabinovici
3Department of Neurology, University of California, San Francisco, San Francisco, California, United States of America
MDHoward J. Rosen
3Department of Neurology, University of California, San Francisco, San Francisco, California, United States of America
MDBruce L. Miller
3Department of Neurology, University of California, San Francisco, San Francisco, California, United States of America
MDBradley T. Hyman
4Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
MD, PhDGerard D. Schellenberg
5Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America
PhDLilah M. Besser
6National Alzheimer’s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
MPHWalter A. Kukull
6National Alzheimer’s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
PhDCeleste M. Karch
7Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA
PhDJames B. Brewer
8Department of Neurosciences, University of California, San Diego, La Jolla, California, United States of America
9Department of Radiology, University of California, San Diego, La Jolla, California, United States of America
10Shiley-Marcos Alzheimer’s Disease Research Center, University of California, San Diego, La Jolla, California, United States of America
MD, PhDKarolina Kauppi
9Department of Radiology, University of California, San Diego, La Jolla, California, United States of America
PhDLinda K. McEvoy
9Department of Radiology, University of California, San Diego, La Jolla, California, United States of America
PhDOle A. Andreassen
11NORMENT Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
MD, PhDAnders M. Dale
8Department of Neurosciences, University of California, San Diego, La Jolla, California, United States of America
9Department of Radiology, University of California, San Diego, La Jolla, California, United States of America
12Department of Cognitive Science, University of California, San Diego, La Jolla, California, United States of America
PhDChun Chieh Fan
12Department of Cognitive Science, University of California, San Diego, La Jolla, California, United States of America
MDRahul S. Desikan
1Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States of America
MD, PhDABSTRACT
Identifying asymptomatic older individuals at elevated risk for developing Alzheimer’s disease (AD) is of clinical importance. Among 1,081 asymptomatic older adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling for APOE ε4 carrier status. Older individuals in the highest PHS percentiles showed the highest AD incidence rates. PHS predicted longitudinal clinical decline among older individuals with moderate to high CERAD (amyloid) and Braak (tau) scores at autopsy, even among APOE ε4 non-carriers. Beyond APOE, PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer’s neurodegeneration.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Posted June 27, 2017.
Polygenic hazard scores in preclinical Alzheimer’s disease
Chin Hong Tan, Leo P. Sugrue, Iris J. Broce, Elizabeth Tong, Jacinth J. X. Tan, Christopher P. Hess, William P. Dillon, Luke W. Bonham, Jennifer S. Yokoyama, Gil D. Rabinovici, Howard J. Rosen, Bruce L. Miller, Bradley T. Hyman, Gerard D. Schellenberg, Lilah M. Besser, Walter A. Kukull, Celeste M. Karch, James B. Brewer, Karolina Kauppi, Linda K. McEvoy, Ole A. Andreassen, Anders M. Dale, Chun Chieh Fan, Rahul S. Desikan
bioRxiv 156331; doi: https://doi.org/10.1101/156331
Polygenic hazard scores in preclinical Alzheimer’s disease
Chin Hong Tan, Leo P. Sugrue, Iris J. Broce, Elizabeth Tong, Jacinth J. X. Tan, Christopher P. Hess, William P. Dillon, Luke W. Bonham, Jennifer S. Yokoyama, Gil D. Rabinovici, Howard J. Rosen, Bruce L. Miller, Bradley T. Hyman, Gerard D. Schellenberg, Lilah M. Besser, Walter A. Kukull, Celeste M. Karch, James B. Brewer, Karolina Kauppi, Linda K. McEvoy, Ole A. Andreassen, Anders M. Dale, Chun Chieh Fan, Rahul S. Desikan
bioRxiv 156331; doi: https://doi.org/10.1101/156331
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