GWAS for Early Onset Coronary Disease (ADVANCE)

ADVANCE (Atherosclerotic Disease, VAscular functioN, and genetiC Epidemiology) is a large epidemiological study of genetic and non-genetic determinants of coronary artery disease (CAD) that started in 2000 as a collaborative effort between researchers at Stanford University and Kaiser Permanente of Northern California. The overarching goal of the study is to improve our ability to prevent, diagnose and treat CAD. The initial study included recruitment of over 3600 subjects (including 1873 subjects with incident clinically significant coronary disease and 1745 control subjects) from multiple race/ethnic backgrounds. A subset of ~ 500 subjects with very early onset coronary disease (men < 45 and women < 55) and ~ 500 similar aged controls were genotyped using the Illumina 550K platform as part of an NIH funded effort within the STAMPEED consortium.]]>
This analysis is a GWAS for coronary artery disease among European Americans in the ADVANCE study. The case-control analysis was performed with age and gender as covariates. All genotypes were generated on Illumina 550K arrays.Cases Inclusion Evidence in the electronic databases of any of the following in the time period 1/1/1999-12/31/2003: a rise in cardiac enzymes with a discharge diagnosis of CAD, a coronary revascularization procedure, or a diagnosis of angina with a coronary angiogram documenting at least one stenosis > 50%. Age on date of first hospitalization for qualifying event: 18 to 45 for males, 18 to 55 for females Exclusion Evidence in the electronic databases (going back to 01/01/1996) of any of the following: CAD related diagnosis at anytime prior to the date of hospitalization, cancer, cirrhosis, renal failure, a bone marrow or organ transplant, entry in "no contact list", no assigned PCP, and remote distance from the study clinics. A report during a screening interview of an inability to speak and write English, or any of the above exclusion criteria except a history of CAD prior to membership in KPNC. Controls Young Controls from Kaiser Inclusion Membership in KPNC continuously since 1/1/1998 Age on 6/30/2003 between 30 and 45 years for males and 30 and 55 years for females Living in Oakland, San Francisco, Berkeley, Emeryville, Piedmont, Richmond or Albany, California Exclusion Evidence in the electronic databases (going back to 01/01/1996) of any of the following: atherosclerotic vascular disease (including CAD, CHF, stroke, PVD, cerebrovascular disease, and vascular disease not otherwise specified), HIV, dementia, cancer, cirrhosis, renal failure, entry in "no contact list", no assigned PCP, and remote distance from the study clinics. A report during a screening interview an inability to speak and write English, or of any of the above exclusion criteria at any time. Young Controls from CARDIA Inclusion Participants in the CARDIA study with white/European and African American ancestry originally recruited in the Oakland KPNC field center in 1985-86 who completed the year 15 examination in 2000-2001 and had adequate samples of DNA. Exclusion A personal history of clinically significant CAD or documented CAD by CARDIA investigators ]]>
With the primary aim of uncovering novel genetic determinants of CAD and of acute myocardial infarction (MI), investigators at Stanford University and Kaiser Permanente of Northern California (KPNC) initiated the ADVANCE study in October 2000. Cases and controls were identified from over 2.9 million enrollees in KPNC, an ethnically diverse population representative of the local and statewide population. Eligible subjects were identified using the KPNC electronic databases and those who agreed to participate were interviewed and examined at one of several clinics in the San Francisco Bay Area. To allow for several pre-specified contrasts, a specialized recruitment strategy was devised. Between October 28, 2001 and December 31, 2003, we assembled a study including over 3,600 subjects with detailed clinical information and blood for DNA and protein studies. ADVANCE Phase I At the time of the ADVANCE Phase I study, there were technological limitations that made it impossible to survey the entire human genome for genetic polymorphisms that are associated with coronary disease. Thus, initially our approach focused on a more limited candidate gene based approach. We selected candidate genes on the basis of results of local genomic experiments and an extensive review of the literature. Single nucleotide polymorphisms (SNPs) were identified in each of the candidate gene loci through a process of SNP discovery, and a subset of these SNPs were genotyped in all participants in the ADVANCE Study to compare case and control groups with the respect to the acquisition or progression of atherosclerotic disease. Details regarding the candidate genes, SNPs and genotyping strategy studied in ADVANCE Phase I are available through the ADVANCE web site. The first phase of ADVANCE was funded through a generous grant from the Donald W. Reynolds Foundation, Las Vegas from October 2000 until June 2006. ADVANCE Phase II In ADVANCE Phase II, we performed a high density GWA scan using over 550,000 SNPs on a population of highly selected and characterized cohort of young individuals with premature CAD from ADVANCE. This phase of ADVANCE is largely being funded by a grant from the NHLBI that will ran from October 1, 2006 through July 31, 2009 as part of the STAMPEED effort. GWA data from the ADVANCE project has been used as part of several large meta-analyses including consortia concerned with coronary disease (CARDIOGRAM) and anthropomorphic traits (GIANT). Through dbGaP, analysis data is available. Individual level genotypic and phenotypic data can be requested through an ancillary study proposal by contacting the ADVANCE Principal Investigator, Dr. Thomas Quertermous at [e-mail].]]>