Macular Degeneration study with SNP/CNV Genotypes (imputed), SNP/CNV Genotypes (NGS) data on dbGaP (35,358 participants)

phs001039 — International AMD Genomics Consortium - Exome Chip Experiment

Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. To further our understanding of AMD genetics, we examined the contribution of common and rare genetic variation in the International AMD Genomics Consortium that included ~50,000 samples of 26 AMD case - control cohorts that were jointly genotyped. Analyzing 16,144 patients with late stage AMD and 17,832 controls, we identified 52 independently associated common and rare variants distributed across 34 loci. Besides these single variant signals, we also observed gene-based enrichment of very rare coding variants (frequency &#x3C; 0.1%) in cases that implicated causal roles for <a href="http://www.ncbi.nlm.nih.gov/gene/3075">CFH</a>, <a href="http://www.ncbi.nlm.nih.gov/gene/3426">CFI</a> and <a href="http://www.ncbi.nlm.nih.gov/gene/7078">TIMP3</a> in three of the known AMD risk loci. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.