Macular Degeneration study on dbGaP (5,653 participants)

phs000684 — Age-Related Macular Degeneration - MMAP Cohort: Association and    Sequencing Studies

Age-related Macular Degeneration (AMD) is a leading cause of incurable blindness in people over the age of 65. AMD is a late-onset multi-factorial neurodegenerative disease and its pathogenesis involves interaction of genetic and environmental factors. Several chromosomal regions have been associated with AMD susceptibility through linkage analysis (<a href="http://www.ncbi.nlm.nih.gov/pubmed/19405847">Swaroop et al., 2009</a>). More recent studies provide strong evidence that variants within the CFH gene cluster on chromosome 1 and at/near LOC387715/ARMS2 on chromosome 10 are strongly associated with the disease. Variants at other genes including C2/BF, C3, CFI and APOE4, also contribute to AMD susceptibility. Our primary goals are to identify genetic variants and haplotypes that are associated with AMD. The underlying hypothesis is that DNA variation(s) in multiple genetic susceptibility loci will predispose individuals to AMD pathogenesis, and comparison of DNA of cases and controls should identify these susceptibility variants. Our studies are focused on the genetic analysis of advanced AMD and should provide novel insights into disease diagnosis, progression and pathology. We have assembled a collaborative group of researchers from the University of Michigan, Mayo Clinic, University of Pennsylvania, and the AREDS group including National Eye Institute intramural investigators, who collected clinical data and DNA from a large number of patients affected with AMD and from unaffected controls. The primary source of funding was National Eye Institute. Study 1: To identify genetic variants and haplotypes that are associated with AMD, we submitted and obtained usable genotyping data on 2185 patients and 1155 controls from the Center for Inherited Disease Research (CIDR). Study 2: To identify rare coding variants associated with a large increase in risk of AMD, 10 candidate loci spanning 57 genes were sequenced in 2,335 cases and 789 controls. Probes were designed to capture 96.5% of the coding sequence and 35% of total locus sequence, generating an average 123Mb of on-target sequence per individual at 127x average depth. Substudies: <li><a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000182">phs000182</a> AMD-MMAP Cohort Study: A Joint Genome-Wide Asscociation Study</li> <li><a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000246">phs000246</a> Fuchs' Corneal Dystrophy GWAS</li> <li><a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000457">phs000457</a> MMAP Methylation in AMD</li> <li><a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000685">phs000685</a> Age-Related Macular Degeneration Targeted Sequencing Study</li>