ONTOLOGY SOURCE REFERENCE
Term Source Name	"CHEBI"	"BTO"	"EFO"	"NCBITAXON"	"OMIM"	"UO"	
Term Source File	"http://data.bioontology.org/ontologies/CHEBI"	"http://data.bioontology.org/ontologies/BTO"	"http://data.bioontology.org/ontologies/EFO"	"http://data.bioontology.org/ontologies/NCBITAXON"	"http://data.bioontology.org/ontologies/OMIM"	"http://data.bioontology.org/ontologies/UO"	
Term Source Version	"78"	"20"	"111"	"2"	"4"	"42"	
Term Source Description	"Chemical Entities of Biological Interest Ontology"	"BRENDA Tissue and Enzyme Source Ontology"	"Experimental Factor Ontology"	"National Center for Biotechnology Information (NCBI) Organismal Classification"	"Online Mendelian Inheritance in Man"	"Units of Measurement Ontology"	
INVESTIGATION
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INVESTIGATION PUBLICATIONS
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STUDY
Study Identifier	"E-GEOD-38511"
Study Title	"Aspirin Exposure Reveals Novel Genes Associated with Platelet Function and Cardiovascular Events (outpatient cardiology)"
Study Description	"Background: Identifying individuals at heightened cardiovascular risk is a priority for reducing the global burden of cardiovascular disease. Aspirin is widely used to prevent cardiovascular events, though with variable results. Therefore, we hypothesized that aspirin exposure would reveal novel biological pathways relevant to the development of cardiovascular events. Methods: We administered aspirin, followed by peripheral blood RNA microarray profiling, in a discovery cohort of healthy volunteers (n = 50, HV1), followed by two validation cohorts of healthy volunteers (n = 53, HV2) or outpatient cardiology (OPC, n = 25) patients, in conjunction with platelet function testing with the platelet functions score (PFS, HV1 and HV2) or the VerifyNow Asprin (VN, OPC) test. Sets of coexpressed genes, or “Factors” were identified via Bayesian sparse factor analysis and associated with platelet function in HV1 and validated in HV2 and OPC. Validated factors were associated with death/MI in observational (n = 191) and case:control (n = 447) patient cohorts with available RNA data collected at the time of cardiac catheterization. Results: Factor analysis yielded 20 Factors, of which one, Factor 14, contained 60 genes and was associated with PFS in HV1 (r = -0.31, p-value = 0.03). Factor 14 was associated with platelet function with the same strength and direction in HV2 (r = -0.34, p-value = 0.02) and OPC (one-sided p-value for aspirin resistant vs. aspirin sensitive = 0.046), thus validating the association. Factor 14 was associated with death/MI in the two patient cohorts, odds ratio (OR) = 1.2, 95% CI [1.02-1.4], p-value = 0.01 and hazard ratio = 1.5, [1.2-1.9], p = 0.001, respectively, independent of known cardiovascular risk factors (combined OR = 1.2, CI = [1.02, 1.4], p = 0.03). Factor 14 and the expression of the Factor 14 transcript most highly correlative of PFS, ITGA2B, improved reclassification compared to traditional risk factors (category-free net reclassification index = 31% and 37%, p ≤ 0.0002 for both). Conclusions: By challenging humans subjects with aspirin, a medication used for cardiovascular risk reduction, we elucidated genes and pathways that may underlie platelet function and mechanisms responsible for cardiovascular death/MI. This accession represents the OPC cohort microarray data 26 subjects selected for microarray analysis were divided into three groups: aspirin resistant (AR, n=8, >550 ARU), high normal (HN, n=9, ARU 500-549) and aspirin sensitive (AS, n=9, ARU<500)"
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Study Public Release Date	"2013-12-06"
Study File Name	"s_E-GEOD-38511_study_samples.txt"
STUDY DESIGN DESCRIPTORS
Study Design Type	"transcription profiling by array"
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STUDY PUBLICATIONS
Study PubMed ID	"23454623"	"23831034"
Study Publication DOI	"10.1016/j.gene.2013.02.032"	"10.1016/j.jacc.2013.05.073"
Study Publication Author List	"Fallahi P, Katz R, Toma I, Li R, Reiner J, VanHouten K, Carpio L, Marshall L, Lian Y, Bupp S, Fu SW, Rickles F, Leitenberg D, Lai Y, Weksler BB, Rebling F, Yang Z, McCaffrey TA"	"Voora D, Cyr D, Lucas J, Chi JT, Dungan J, McCaffrey TA, Katz R, Newby LK, Kraus WE, Becker RC, Ortel TL, Ginsburg GS"
Study Publication Title	"Aspirin insensitive thrombophilia: transcript profiling of blood identifies platelet abnormalities and HLA restriction."	"Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events."
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STUDY FACTORS
Study Factor Name	"group"
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STUDY ASSAYS
Study Assay File Name	"a_E-GEOD-38511_GeneChip_assay.txt"
Study Assay Measurement Type	"transcription profiling"
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Study Assay Technology Type	"DNA microarray"
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STUDY PROTOCOLS
Study Protocol Name	"P-GSE38511-2"	"P-GSE38511-3"	"P-GSE38511-4"	"P-GSE38511-5"	"P-GSE38511-1"
Study Protocol Type	"nucleic acid extraction protocol"	"labeling protocol"	"hybridization protocol"	"array scanning protocol"	"normalization data transformation protocol"
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Study Protocol Description	"Total RNA was purified from whole blood using PAXgene Blood RNA kit (PreAnalytiX), including an on-column DNAse treatment. RNA samples were further purified using RNAeasy Mini kit (Qiagen Sciences)."	"Purified RNA (100 ng) was reversed transcribed with SuperScript III using random hexamers and the cDNA was amplified with Ovation RNA Amplification System V2 kit (NuGEN Technologies). The cDNA was purified with DNA Clean & Concentrator-25 (Zymo Research) and 3.75 ug of cDNA was fragmented and labeled with FL-Ovation cDNA Biotin Module V2 kit (NuGEN Technologies)"	"cDNA was hybridized to an Affymetrix GeneChip Human Genome U133 Plus 2.0 Array for 18 hours"	"The arrays were washed and then fluorescence was quantitated on an Affymetrix GeneChip Scanner 3000 7G."	"RMA normalization in R ID_REF =  VALUE = log2 RMA signal"
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STUDY CONTACTS
Study Person Last Name	"Voora"	"McCaffrey"
Study Person First Name	"Deepak "	"Timothy"
Study Person Mid Initials	""	"A"
Study Person Email	"deepak.voora@duke.edu"	""
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Study Person Address	"Institute for Genome Sciences & Policy, Duke University, 905 S. Lasalle St, 2004 Snyderman Building, DUMC 3445, Durham, NC, USA"	""
Study Person Affiliation	"Duke University"	""
Study Person Roles	"submitter"	""
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