ID

45817

Beskrivning

Principal Investigator: Lewis C. Becker, MD, Johns Hopkins University School of Medicine, Baltimore, MD, USA MeSH: Platelet Aggregation,Blood Physiological Phenomena,Cardiovascular Physiological Phenomena https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001074 The causal mechanisms of common diseases and their therapies have been only marginally illuminated by genetic variants identified in genome wide association studies (GWAS) utilizing single nucleotide polymorphism (SNPs). Platelet activation pathways reflecting hemostasis and thrombosis are the underlying substrate for many cardiovascular diseases and related acute events. To overcome GWAS limitations, genomic studies are needed that integrate molecular surrogates for platelet-related phenotypes assayed in cell-based models derived from individuals of known genotypes and phenotypes. In our GWAS study of native platelet aggregation phenotypes and aggregation in response to low dose aspirin in 2200 subjects (GeneSTAR, Genetic Study of Aspirin Responsiveness), important genome wide "signals" (p5x10-8) associated with native platelet aggregation and important "signals" associated with platelet responsiveness to aspirin were identified and replicated. Although we are currently performing functional genomics studies to elucidate our most promising findings in known genes (PEAR1, MET, PIKC3G), most "signals" occurred in intergenic regions or in introns. Mechanistic interpretation is limited by uncertainty as to which gene(s) are up- or down-regulated in the presence of most SNP modifications. In this 3 phase proposal, we will (1) create pluripotent stem cells (iPS) from peripheral blood mononuclear cells, and then differentiate these stem cells into megakaryocytes (2) develop an efficient strategy to produce iPS and megakaryocytes using a novel pooling method, and (3) produce iPS and megakaryocytes from 250 subjects in GeneSTAR (European Americans and African Americans), selected based on specific hypotheses derived from GWAS signals in native and post aspirin platelet function; characterize genetic mRNA transcripts using a comprehensive Affymetrix array; measure protein expression for transcripts of interest using mass spectrometry; examine mRNA and protein expression patterns for each GWAS signal to determine the functional pathway(s) involved in native platelet phenotypes; and examine the functional genomics of variations in responsiveness to aspirin using our prior genotyped and phenotyped population. Precise information about the exact functional processes in megakaryocytes and platelets may lead to innovative and tailored approaches to risk assessment and novel therapeutic targets to prevent first and recurrent cardiovascular and related thrombotic events.

Länk

dbGaP study = phs001074

Nyckelord

Versioner (1)
  1. 2023-06-29 2023-06-29 - Simon Heim
Rättsinnehavare

Lewis C. Becker, MD, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Uppladdad den

29 juni 2023

DOI

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Licens

Creative Commons BY 4.0
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dbGaP phs001074 GeneSTAR NextGen Functional Genomics of Platelet Aggregation

Engelsk

Eligibility Criteria

6 Formulär  
  1. StudyEvent: SEV1
    1. Eligibility Criteria
    2. The subject consent file includes subject IDs and their consent group information.
    3. The pedigree table includes family ID, subject ID, father and mother ID, and subject gender, to link subjects of the same family.
    4. This subject sample mapping file contains a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
    5. The subject phenotype table includes age, sex, race, visit number, BMI, hypertension status (n=4 variables; self-reported, measured blood pressure, and medication), diabetic status (n=2 variables; glucose levels and medication), lipid measurements (n=4 variables; TC, TG, HDL, and LDL), cbc measurements (n=23 variables), whole blood measurements (n=22 variables; arachidonic acid, ADP/ATP, collagen/epineprhine/thromboxane B2, aggregation, all corrected for platelet counts), platelet rich plasma measurements (n=47 variables; arachidonic acid, ADP/ATP, collagen/epineprhine/thromboxane B2, aggregation, all corrected for platelet counts), urine measurements (n=1 variable; thromboxane B2 adjusted for urinary creatinine), and current smoking status.
    6. The sample attributes table includes body site where sample was collected, analyte type, tumor status, and genotyping center.
Inclusion and exclusion criteria
Beskrivning

Inclusion and exclusion criteria

Alias
UMLS CUI [1,1]
C1512693
UMLS CUI [1,2]
C0680251
Subjects were included if they were members of the original GeneSTAR Study population and were over 21 years of age. Subjects were excluded if they developed diabetes, cardiovascular disease, and any new known bleeding disorder, AIDS, advanced cancer, cancer under treatment or autoimmune diseases. Women who were pregnant when first recruited with consent will be deferred until 6 months after delivery, so they were not excluded, but did not give a blood sample during their pregnancy. Subjects with certain conditions that might be influenced by taking a 100cc volume of blood have already been pre-screened in GeneSTAR and were not eligible if they had blood dyscrasias, anemia, bleeding disorder or any contraindications to phlebotomy.
Beskrivning

Subjects were included if they were members of the original GeneSTAR Study population and were over 21 years of age. Subjects were excluded if they developed diabetes, cardiovascular disease, and any new known bleeding disorder, AIDS, advanced cancer, cancer under treatment or autoimmune diseases. Women who were pregnant when first recruited with consent will be deferred until 6 months after delivery, so they were not excluded, but did not give a blood sample during their pregnancy. Subjects with certain conditions that might be influenced by taking a 100cc volume of blood have already been pre-screened in GeneSTAR and were not eligible if they had blood dyscrasias, anemia, bleeding disorder or any contraindications to phlebotomy.

Datatyp

boolean

Alias
UMLS CUI [1,1]
C0681850
UMLS CUI [1,2]
C1512693
UMLS CUI [1,3]
C2348561
UMLS CUI [1,4]
C0001779
UMLS CUI [2,1]
C2828389
UMLS CUI [2,2]
C1334965
UMLS CUI [2,3]
C0011849
UMLS CUI [2,4]
C0007222
UMLS CUI [2,5]
C0005779
UMLS CUI [2,6]
C0001175
UMLS CUI [2,7]
C0877373
UMLS CUI [2,8]
C0920425
UMLS CUI [2,9]
C0004364
UMLS CUI [3,1]
C0033011
UMLS CUI [3,2]
C2949735
UMLS CUI [3,3]
C0021430
UMLS CUI [3,4]
C0205421
UMLS CUI [3,5]
C4699371
UMLS CUI [4,1]
C0871117
UMLS CUI [4,2]
C4086268
UMLS CUI [4,3]
C0190979
UMLS CUI [4,4]
C1555471
UMLS CUI [4,5]
C0018939
UMLS CUI [4,6]
C0002871
UMLS CUI [4,7]
C0005779
UMLS CUI [4,8]
C0522473
UMLS CUI [4,9]
C0005857
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Similar models

Eligibility Criteria

6 Formulär
  1. StudyEvent: SEV1
    1. Eligibility Criteria
    2. The subject consent file includes subject IDs and their consent group information.
    3. The pedigree table includes family ID, subject ID, father and mother ID, and subject gender, to link subjects of the same family.
    4. This subject sample mapping file contains a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
    5. The subject phenotype table includes age, sex, race, visit number, BMI, hypertension status (n=4 variables; self-reported, measured blood pressure, and medication), diabetic status (n=2 variables; glucose levels and medication), lipid measurements (n=4 variables; TC, TG, HDL, and LDL), cbc measurements (n=23 variables), whole blood measurements (n=22 variables; arachidonic acid, ADP/ATP, collagen/epineprhine/thromboxane B2, aggregation, all corrected for platelet counts), platelet rich plasma measurements (n=47 variables; arachidonic acid, ADP/ATP, collagen/epineprhine/thromboxane B2, aggregation, all corrected for platelet counts), urine measurements (n=1 variable; thromboxane B2 adjusted for urinary creatinine), and current smoking status.
    6. The sample attributes table includes body site where sample was collected, analyte type, tumor status, and genotyping center.
Name
Typ
Description | Question | Decode (Coded Value)
Datatyp
Alias
Item Group
Inclusion and exclusion criteria
C1512693 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
Subjects were included if they were members of the original GeneSTAR Study population and were over 21 years of age. Subjects were excluded if they developed diabetes, cardiovascular disease, and any new known bleeding disorder, AIDS, advanced cancer, cancer under treatment or autoimmune diseases. Women who were pregnant when first recruited with consent will be deferred until 6 months after delivery, so they were not excluded, but did not give a blood sample during their pregnancy. Subjects with certain conditions that might be influenced by taking a 100cc volume of blood have already been pre-screened in GeneSTAR and were not eligible if they had blood dyscrasias, anemia, bleeding disorder or any contraindications to phlebotomy.
Item
Subjects were included if they were members of the original GeneSTAR Study population and were over 21 years of age. Subjects were excluded if they developed diabetes, cardiovascular disease, and any new known bleeding disorder, AIDS, advanced cancer, cancer under treatment or autoimmune diseases. Women who were pregnant when first recruited with consent will be deferred until 6 months after delivery, so they were not excluded, but did not give a blood sample during their pregnancy. Subjects with certain conditions that might be influenced by taking a 100cc volume of blood have already been pre-screened in GeneSTAR and were not eligible if they had blood dyscrasias, anemia, bleeding disorder or any contraindications to phlebotomy.
boolean
C0681850 (UMLS CUI [1,1])
C1512693 (UMLS CUI [1,2])
C2348561 (UMLS CUI [1,3])
C0001779 (UMLS CUI [1,4])
C2828389 (UMLS CUI [2,1])
C1334965 (UMLS CUI [2,2])
C0011849 (UMLS CUI [2,3])
C0007222 (UMLS CUI [2,4])
C0005779 (UMLS CUI [2,5])
C0001175 (UMLS CUI [2,6])
C0877373 (UMLS CUI [2,7])
C0920425 (UMLS CUI [2,8])
C0004364 (UMLS CUI [2,9])
C0033011 (UMLS CUI [3,1])
C2949735 (UMLS CUI [3,2])
C0021430 (UMLS CUI [3,3])
C0205421 (UMLS CUI [3,4])
C4699371 (UMLS CUI [3,5])
C0871117 (UMLS CUI [4,1])
C4086268 (UMLS CUI [4,2])
C0190979 (UMLS CUI [4,3])
C1555471 (UMLS CUI [4,4])
C0018939 (UMLS CUI [4,5])
C0002871 (UMLS CUI [4,6])
C0005779 (UMLS CUI [4,7])
C0522473 (UMLS CUI [4,8])
C0005857 (UMLS CUI [4,9])
Tillbaka till toppen 

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