Seven new loci associated with age-related macular degeneration

Lars G Fritsche; Wei Chen; Matthew Schu; Brian L Yaspan; Yi Yu; Gudmar Thorleifsson; Donald J Zack; Satoshi Arakawa; Valentina Cipriani; Stephan Ripke; Robert P Igo; Gabriëlle H S Buitendijk; Xueling Sim; Daniel E Weeks; Robyn H Guymer; Joanna E Merriam; Peter J Francis; Gregory Hannum; Anita Agarwal; Ana Maria Armbrecht; Isabelle Audo; Tin Aung; Gaetano R Barile; Mustapha Benchaboune; Alan C Bird; Paul N Bishop; Kari E Branham; Matthew Brooks; Alexander J Brucker; William H Cade; Melinda S Cain; Peter A Campochiaro; Chi-Chao Chan; Ching-Yu Cheng; Emily Y Chew; Kimberly A Chin; Itay Chowers; David G Clayton; Radu Cojocaru; Yvette P Conley; Belinda K Cornes; Mark J Daly; Baljean Dhillon; Albert O Edwards; Evangelos Evangelou; Jesen Fagerness; Henry A Ferreyra; James S Friedman; Asbjorg Geirsdottir; Giuliana Silvestri; The AMD Gene Consortium

doi:10.1038/ng.2578

Seven new loci associated with age-related macular degeneration

Lars G Fritsche, Wei Chen, Matthew Schu, Brian L Yaspan, Yi Yu, Gudmar Thorleifsson, Donald J Zack, Satoshi Arakawa, Valentina Cipriani, Stephan Ripke, Robert P Igo, Gabriëlle H S Buitendijk, Xueling Sim, Daniel E Weeks, Robyn H Guymer, Joanna E Merriam, Peter J Francis, Gregory Hannum, Anita Agarwal, Ana Maria ArmbrechtIsabelle Audo, Tin Aung, Gaetano R Barile, Mustapha Benchaboune, Alan C Bird, Paul N Bishop, Kari E Branham, Matthew Brooks, Alexander J Brucker, William H Cade, Melinda S Cain, Peter A Campochiaro, Chi-Chao Chan, Ching-Yu Cheng, Emily Y Chew, Kimberly A Chin, Itay Chowers, David G Clayton, Radu Cojocaru, Yvette P Conley, Belinda K Cornes, Mark J Daly, Baljean Dhillon, Albert O Edwards, Evangelos Evangelou, Jesen Fagerness, Henry A Ferreyra, James S Friedman, Asbjorg Geirsdottir, Giuliana Silvestri, The AMD Gene Consortium

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671 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	433-439
Number of pages	7
Journal	Nature Genetics
Volume	45
Issue number	4
Early online date	03 Mar 2013
DOIs	https://doi.org/10.1038/ng.2578
Publication status	Published - Apr 2013

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Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Buitendijk, G. H. S., Sim, X., Weeks, D. E., Guymer, R. H., Merriam, J. E., Francis, P. J., Hannum, G., Agarwal, A., ... The AMD Gene Consortium (2013). Seven new loci associated with age-related macular degeneration. Nature Genetics, 45(4), 433-439. https://doi.org/10.1038/ng.2578

@article{f224171bc5384f51bd886bb525adc613,

title = "Seven new loci associated with age-related macular degeneration",

abstract = "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.",

author = "Fritsche, {Lars G} and Wei Chen and Matthew Schu and Yaspan, {Brian L} and Yi Yu and Gudmar Thorleifsson and Zack, {Donald J} and Satoshi Arakawa and Valentina Cipriani and Stephan Ripke and Igo, {Robert P} and Buitendijk, {Gabri{\"e}lle H S} and Xueling Sim and Weeks, {Daniel E} and Guymer, {Robyn H} and Merriam, {Joanna E} and Francis, {Peter J} and Gregory Hannum and Anita Agarwal and Armbrecht, {Ana Maria} and Isabelle Audo and Tin Aung and Barile, {Gaetano R} and Mustapha Benchaboune and Bird, {Alan C} and Bishop, {Paul N} and Branham, {Kari E} and Matthew Brooks and Brucker, {Alexander J} and Cade, {William H} and Cain, {Melinda S} and Campochiaro, {Peter A} and Chi-Chao Chan and Ching-Yu Cheng and Chew, {Emily Y} and Chin, {Kimberly A} and Itay Chowers and Clayton, {David G} and Radu Cojocaru and Conley, {Yvette P} and Cornes, {Belinda K} and Daly, {Mark J} and Baljean Dhillon and Edwards, {Albert O} and Evangelos Evangelou and Jesen Fagerness and Ferreyra, {Henry A} and Friedman, {James S} and Asbjorg Geirsdottir and Giuliana Silvestri and {The AMD Gene Consortium}",

year = "2013",

month = apr,

doi = "10.1038/ng.2578",

language = "English",

volume = "45",

pages = "433--439",

journal = "Nature Genetics",

publisher = "Nature Publishing Group",

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}

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, Silvestri, G & The AMD Gene Consortium 2013, 'Seven new loci associated with age-related macular degeneration', Nature Genetics, vol. 45, no. 4, pp. 433-439. https://doi.org/10.1038/ng.2578

TY - JOUR

T1 - Seven new loci associated with age-related macular degeneration

AU - Fritsche, Lars G

AU - Chen, Wei

AU - Schu, Matthew

AU - Yaspan, Brian L

AU - Yu, Yi

AU - Thorleifsson, Gudmar

AU - Zack, Donald J

AU - Arakawa, Satoshi

AU - Cipriani, Valentina

AU - Ripke, Stephan

AU - Igo, Robert P

AU - Buitendijk, Gabriëlle H S

AU - Sim, Xueling

AU - Weeks, Daniel E

AU - Guymer, Robyn H

AU - Merriam, Joanna E

AU - Francis, Peter J

AU - Hannum, Gregory

AU - Agarwal, Anita

AU - Armbrecht, Ana Maria

AU - Audo, Isabelle

AU - Aung, Tin

AU - Barile, Gaetano R

AU - Benchaboune, Mustapha

AU - Bird, Alan C

AU - Bishop, Paul N

AU - Branham, Kari E

AU - Brooks, Matthew

AU - Brucker, Alexander J

AU - Cade, William H

AU - Cain, Melinda S

AU - Campochiaro, Peter A

AU - Chan, Chi-Chao

AU - Cheng, Ching-Yu

AU - Chew, Emily Y

AU - Chin, Kimberly A

AU - Chowers, Itay

AU - Clayton, David G

AU - Cojocaru, Radu

AU - Conley, Yvette P

AU - Cornes, Belinda K

AU - Daly, Mark J

AU - Dhillon, Baljean

AU - Edwards, Albert O

AU - Evangelou, Evangelos

AU - Fagerness, Jesen

AU - Ferreyra, Henry A

AU - Friedman, James S

AU - Geirsdottir, Asbjorg

AU - Silvestri, Giuliana

AU - The AMD Gene Consortium

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

U2 - 10.1038/ng.2578

DO - 10.1038/ng.2578

M3 - Article

C2 - 23455636

VL - 45

SP - 433

EP - 439

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Seven new loci associated with age-related macular degeneration

Abstract

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