Genetic Control of Human Brain Transcript Expression in Alzheimer Disease

Jennifer A Webster; J. Raphael Gibbs; Jennifer Clarke; Monika Ray; Weixiong Zhang; Peter Holmans; Kristen Rohrer; Alice Zhao; Lauren Marlowe; Mona Kaleem; Donald S McCorquodale; Cindy Cuello; Doris Leung; Leslie Bryden; Priti Nath; Victoria L Zismann; Keta Joshipura; Matthew J Huentelman; Diane Hu-Lince; Keith D Coon; David W Craig; John V Pearson; Christopher B Heward; Eric M Reiman; Dietrich Stephan; John Hardy; Amanda J Myers

doi:10.1016/j.ajhg.2009.03.011

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Genetic Control of Human Brain Transcript Expression in Alzheimer Disease

Journal article

Open access

Peer reviewed

Genetic Control of Human Brain Transcript Expression in Alzheimer Disease

Jennifer A Webster, J. Raphael Gibbs, Jennifer Clarke, Monika Ray, Weixiong Zhang, Peter Holmans, Kristen Rohrer, Alice Zhao, Lauren Marlowe, Mona Kaleem, …

American journal of human genetics, Vol.84(4), pp.445-458

2009

DOI: https://doi.org/10.1016/j.ajhg.2009.03.011

PMCID: PMC2667989

PMID: 19361613

Abstract

We recently surveyed the relationship between the human brain transcriptome and genome in a series of neuropathologically normal postmortem samples. We have now analyzed additional samples with a confirmed pathologic diagnosis of late-onset Alzheimer disease (LOAD; final n = 188 controls, 176 cases). Nine percent of the cortical transcripts that we analyzed had expression profiles correlated with their genotypes in the combined cohort, and approximately 5% of transcripts had SNP-transcript relationships that could distinguish LOAD samples. Two of these transcripts have been previously implicated in LOAD candidate-gene SNP-expression screens. This study shows how the relationship between common inherited genetic variants and brain transcript expression can be used in the study of human brain disorders. We suggest that studying the transcriptome as a quantitative endo-phenotype has greater power for discovering risk SNPs influencing expression than the use of discrete diagnostic categories such as presence or absence of disease.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.57 Alzheimer's Disease
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics

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Details

Title: Genetic Control of Human Brain Transcript Expression in Alzheimer Disease
Creators: Jennifer A Webster - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
J. Raphael Gibbs - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Jennifer Clarke - Department of Epidemiology and Public Health, University of Miami School of Medicine, Clinical Research Building, Miller School of Medicine, Miami, FL 33133, USA
Monika Ray - Department of Computer Science and Engineering, Washington University, St. Louis, MO 63130, USA
Weixiong Zhang - Department of Computer Science and Engineering, Washington University, St. Louis, MO 63130, USA
Peter Holmans - Biostatistics and Bioinformatics Unit, Department of Psychological Medicine, Cardiff University, Cardiff, Wales CF14 4XN, UK
Kristen Rohrer - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Alice Zhao - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Lauren Marlowe - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Mona Kaleem - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Donald S McCorquodale - Department of Psychiatry and Behavioral Sciences, Division of Neuroscience, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
Cindy Cuello - Department of Psychiatry and Behavioral Sciences, Division of Neuroscience, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
Doris Leung - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Leslie Bryden - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Priti Nath - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Victoria L Zismann - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Keta Joshipura - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Matthew J Huentelman - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Diane Hu-Lince - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Keith D Coon - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
David W Craig - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
John V Pearson - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Christopher B Heward - Kronos Science Laboratory, Phoenix, AZ 85016, USA
Eric M Reiman - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Dietrich Stephan - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
John Hardy - Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Amanda J Myers - Department of Psychiatry and Behavioral Sciences, Division of Neuroscience, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
Publication Details: American journal of human genetics, Vol.84(4), pp.445-458
Publisher: Elsevier Inc
Academic Unit: Miller School of Medicine; Cell Biology Research
Language: English
Resource Type: Journal article
PMID: 19361613
PMCID: PMC2667989
Record Identifier: 991031561077302976