Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study

CHD is the leading cause of death in the United States. One of the most common ways to prevent CHD is to take an anti-platelet agent, which lessens platelet aggregation. Two of the most common anti-platelet agents are aspirin and clopidogrel. However, up to 25% to 30% of people do not respond to these medications. Evidence indicates that treatment response may be related to genetics. The purpose of this study is to determine specific gene variants that predict response to aspirin and clopidogrel therapy. This study is part of a larger group of studies called the Pharmacogenomics Research Network (PGRN). Participants are from the Old Order Amish of Lancaster, Pennsylvania. They are well suited for genetic studies because they are a homogenous, closed, founder population. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before and after clopidogrel alone, and then again after taking clopidogrel plus aspirin. Using the gene variation profiles across the genome, researchers analyzed which variants correspond to treatment response.]]>
JAMA Article SupplementsAssociation of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapyClinic SOPsResearch Consent FormResearch PlanPAPI Flow Sheet for Clinic Visit IPAPI Flow Sheet for Clinic Visit I - Data DictionaryPAPI Flow Sheet for Clinic Visit IIPAPI Flow Sheet for Clinic Visit II - Data DictionaryPAPI Inclusion / Exclusion Criteria for Each InterventionPAPI Inclusion / Exclusion Criteria - Data DictionaryPAPI LifestylePAPI Lifestyle - Data DictionaryPAPI Medical HistoryPAPI Medical History - Data DictionaryPAPI MedicationsPAPI Medications - Data DictionaryTable of PhenotypesInstitutional ApprovalThese genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..These genome-wide association analyses of platelet aggregation phenotypes were conducted as part of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study. Participants are from the Old Order Amish of Lancaster, Pennsylvania. Participants received 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants took a single dose of 324 mg aspirin. Participants underwent platelet function tests before (pre-clopidogrel/pre-aspirin) and after (post-clopidogrel/pre-aspirin) clopidogrel alone, and then again after taking clopidogrel plus aspirin (post-clopidogrel/post-aspirin). Participants were free of clinical cardiovascular disease, consented to use of their DNA for genetic research, and were successfully genotyped on the Affymetrix 500K or Affymetrix 6.0 genome-wide SNP array. Genotyping was conducted at the University of Maryland, Baltimore..Inclusion Criteria: Of Old Order Amish descent At least 20 years old Exclusion Criteria: Currently pregnant or less than 6 months have passed since delivery History of a bleeding disorder or major spontaneous bleed, such as peptic ulcer, epistasis, or intracranial bleed Severe hypertension, defined by a blood pressure above 160/95 mm Hg, making it unethical not to recommend prompt treatment Medications that would affect the outcome(s) to be measured and cannot willingly and safely, in the opinion of the treating physician and study physician, discontinue these medications for 1 week prior to protocol initiation Vitamins or other supplements and is unwilling to discontinue their use for at least 1 week prior to study Coexisting malignancy Creatinine level greater than 2.0 mg/dl, aspartate transaminase (AST) or alanine transaminase (ALT) greater than two times the upper limit of normal, hematocrit less than 32%, or a thyroid-stimulating hormone (TSH) less than 0.4 or greater than 5.5 mIU/L Bleeding disorder or history of gastrointestinal bleeding or other major bleeding episode Currently taking aspirin, clopidogrel, or other anti-coagulant, such as warfarin, heparin, or GPIIb/IIIa antagonists, and have conditions that might place them at increased risk from withdrawal of these medications 14 days prior to protocol initiation, including history of unstable angina, heart attack, angioplasty (including stent placement), coronary artery bypass surgery, atrial fibrillation, stroke or transient ischemic attacks, diabetes, or deep vein thrombosis or other thrombosis Polycythemia, or thrombocytosis, defined by a platelet count greater than 500,000 Thrombocytopenia, defined by a platelet count less than 75,000 Surgery within the last 6 months Aspirin or clopidogrel allergy Currently breast feeding ]]>
The PAPI Study began in August 2006. Old Order Amish in Lancaster County who had participated in Dr. Shuldiner's HAPI Heart Study were recruited. Recruitment was liberalized to include family members of HAPI Heart participants. In 2008 we completed the first genome-wide association study (GWAS) of clopidogrel response in the first 420 PAPI Study participants. This work was published in JAMA on August 25, 2009. Recruitment of the entire cohort, 676 individuals was completed in August 2010. GWAS genotyping (Affymetrics 6.0) was completed in the fall 2010. After data cleaning, we completed our first pass GWAS in February 2011.]]>