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Genetic control of human brain transcript expression in Alzheimer disease.

TitleGenetic control of human brain transcript expression in Alzheimer disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsWebster, JA, J Gibbs, R, Clarke, J, Ray, M, Zhang, W, Holmans, P, Rohrer, K, Zhao, A, Marlowe, L, Kaleem, M, McCorquodale, DS, Cuello, C, Leung, D, Bryden, L, Nath, P, Zismann, VL, Joshipura, K, Huentelman, MJ, Hu-Lince, D, Coon, KD, Craig, DW, Pearson, JV, Heward, CB, Reiman, EM, Stephan, D, Hardy, J, Myers, AJ
Corporate AuthorsNACC-Neuropathology Group
JournalAm J Hum Genet
Volume84
Issue4
Pagination445-58
Date Published2009 Apr
ISSN1537-6605
KeywordsAge of Onset, Aged, Alzheimer Disease, Brain, Case-Control Studies, Female, Gene Expression Profiling, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Transcription Initiation Site, Transcription, Genetic
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.

DOI10.1016/j.ajhg.2009.03.011
Alternate JournalAm. J. Hum. Genet.
PubMed ID19361613
PubMed Central IDPMC2667989
Grant ListG0701075 / / Medical Research Council / United Kingdom
U01 AG016976 / AG / NIA NIH HHS / United States
P30 AG019610 / AG / NIA NIH HHS / United States
G0801418 / / Medical Research Council / United Kingdom
R01 NS059873 / NS / NINDS NIH HHS / United States