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Sleep-wake disorders in Alzheimer’s disease: further genetic analyses in relation to objective sleep measures

Published online by Cambridge University Press:  19 November 2019

Jerome A. Yesavage ,
Art Noda ,
Alesha Heath ,
M. Windy McNerney ,
Benjamin W. Domingue ,
Yozen Hernandez ,
Gary Benson ,
Joachim Hallmayer ,
Ruth O’Hara  and
Leanne M. Williams
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Jerome A. Yesavage*
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Art Noda
Affiliation:
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Alesha Heath
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
M. Windy McNerney
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Benjamin W. Domingue
Affiliation:
Graduate School of Education, Stanford University, Stanford, CA, USA
Yozen Hernandez
Affiliation:
Graduate Program in Bioinformatics, Laboratory for Biocomputing and Informatics, Department of Computer Science, Boston University, Boston, MA, USA
Gary Benson
Affiliation:
Graduate Program in Bioinformatics, Laboratory for Biocomputing and Informatics, Department of Computer Science, Boston University, Boston, MA, USA
Joachim Hallmayer
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Ruth O’Hara
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Leanne M. Williams
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Andrea N. Goldstein-Piekarski
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Jamie M. Zeitzer
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
J. Kaci Fairchild
Affiliation:
Department of Veterans Affairs, Sierra-Pacific MIRECC, Palo Alto, CA, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
*
Correspondence should be addressed to: Jerome A. Yesavage, Director, VISN21 MIRECC, Department of Veterans Affairs, Professor of Psychiatry, Department of Psychiatry, Stanford University School of Medicine, 3801 Miranda Avenue, Palo Alto, CA 94304, USA. Email: yesavage@stanford.edu.
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Abstract

This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer’s disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.

Keywords

sleepAlzheimer’s diseasegeneticscircadian rhythmwake after sleep onsetpolygenic risk scores and variable number tandem repeat
Type
Brief Report
Information
International Psychogeriatrics , Volume 32 , Issue 7: Issue Theme: Sleep and Sleep Disorders in Older Adults , July 2020 , pp. 807 - 813
Copyright
© International Psychogeriatric Association 2019

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