Seven new loci associated with age-related macular degeneration.
Fritsche LG., Chen W., Schu M., Yaspan BL., Yu Y., Thorleifsson G., Zack DJ., Arakawa S., Cipriani V., Ripke S., Igo RP., Buitendijk GHS., Sim X., Weeks DE., Guymer RH., Merriam JE., Francis PJ., Hannum G., Agarwal A., Armbrecht AM., Audo I., Aung T., Barile GR., Benchaboune M., Bird AC., Bishop PN., Branham KE., Brooks M., Brucker AJ., Cade WH., Cain MS., Campochiaro PA., Chan C-C., Cheng C-Y., Chew EY., Chin KA., Chowers I., Clayton DG., Cojocaru R., Conley YP., Cornes BK., Daly MJ., Dhillon B., Edwards AO., Evangelou E., Fagerness J., Ferreyra HA., Friedman JS., Geirsdottir A., George RJ., Gieger C., Gupta N., Hagstrom SA., Harding SP., Haritoglou C., Heckenlively JR., Holz FG., Hughes G., Ioannidis JPA., Ishibashi T., Joseph P., Jun G., Kamatani Y., Katsanis N., N Keilhauer C., Khan JC., Kim IK., Kiyohara Y., Klein BEK., Klein R., Kovach JL., Kozak I., Lee CJ., Lee KE., Lichtner P., Lotery AJ., Meitinger T., Mitchell P., Mohand-Saïd S., Moore AT., Morgan DJ., Morrison MA., Myers CE., Naj AC., Nakamura Y., Okada Y., Orlin A., Ortube MC., Othman MI., Pappas C., Park KH., Pauer GJT., Peachey NS., Poch O., Priya RR., Reynolds R., Richardson AJ., Ripp R., Rudolph G., Ryu E., Sahel J-A., Schaumberg DA., Scholl HPN., Schwartz SG., Scott WK., Shahid H., Sigurdsson H., Silvestri G., Sivakumaran TA., Smith RT., Sobrin L., Souied EH., Stambolian DE., Stefansson H., Sturgill-Short GM., Takahashi A., Tosakulwong N., Truitt BJ., Tsironi EE., Uitterlinden AG., van Duijn CM., Vijaya L., Vingerling JR., Vithana EN., Webster AR., Wichmann H-E., Winkler TW., Wong TY., Wright AF., Zelenika D., Zhang M., Zhao L., Zhang K., Klein ML., Hageman GS., Lathrop GM., Stefansson K., Allikmets R., Baird PN., Gorin MB., Wang JJ., Klaver CCW., Seddon JM., Pericak-Vance MA., Iyengar SK., Yates JRW., Swaroop A., Weber BHF., Kubo M., Deangelis MM., Léveillard T., Thorsteinsdottir U., Haines JL., Farrer LA., Heid IM., Abecasis GR., AMD Gene Consortium None.
Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.