Grant Detail
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Genomic Architecture of Progression and Treatment Response in AMD
15 June 2000 - 31 July 2016
NATIONAL EYE INSTITUTE
Total Funding: $ 5,944,111
DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is a significant health problem that affects millions of individuals and is the most common cause of severe vision loss among individuals over age 50 in the U.S. (Rein et al. 2006). The influence of genetic variation on AMD is strong and through the application of recent technological advances the genetic etiology of risk for AMD is being deconstructed. Independent studies, including our own, have identified and confirmed variations in multiple genes that affect risk to AMD, including CFH, HTRA1/ARMS2, C2/CFB, and C3 (DeAngelis et al. 2007;Edwards et al. 2005;Haines et al. 2005;Jakobsdottir et al. 2005;Klein et al. 2005;Maller et al. 2006;Rivera et al. 2005;Schaumberg et al. 2007;Schmidt et al. 2006;Hageman et al. 2005;Yates et al. 2007;Maller et al. 2007). Variation in these genes explain a significant portion of the genetic risk for AMD and ongoing studies are continuing to identify additional such genes. Also important are environmental risk factors such as smoking, hormone therapy and diet that contribute to AMD risk both independently and through their interactions with genes (Schmidt et al. 2006;Schaumberg et al. 2007;Wang et al. 2009). Again, ongoing studies are teasing apart these contributions. However, risk is just one of the many facets of the overall genetic architecture of AMD. Disease progression and treatment response are two critical elements also influenced by genetic variation (Shuler, Jr. et al. 2007;Seddon et al. 2007;Francis et al. 2009). The goal of this proposal is to increase our understanding of the genetic etiology of progression and treatment response in AMD, both of which have been understudied. Identifying the genes underlying clinical outcomes is directly relevant to better directing current treatments and developing new and better treatments and regimens for those suffering this disabling disorder. PUBLIC HEALTH RELEVANCE: Age-related macular degeneration (AMD) is a significant health problem that affects millions of individuals and is the most common cause of severe vision loss among individuals over age 50 in the U.S. The goal of this proposal is to increase our understanding of the genetic etiology of progression and treatment response in AMD, both of which have been understudied. Identifying the genes underlying clinical outcomes is directly relevant to better directing current treatments and developing new and better treatments and regimens for those suffering this disabling disorder.
36 Resulting Publications
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1.
2012Stephen G Schwartz; Anita Agarwal; Jaclyn L Kovach; Paul J Gallins; William Cade; Eric A Postel; Gaofeng Wang; Juan Ayala-Haedo; Kylee M Spencer; Jonathan L Haines; et al.
The ARMS2 A69S variant and bilateral advanced age-related macular degeneration.
Retina (Philadelphia, Pa.) 2012;32(8):1486-91. -
2.
2012Megan Ulmer; Jun Li; Brian L Yaspan; Ayse Bilge Ozel; Julia E Richards; Sayoko E Moroi; Felicia Hawthorne; Donald L Budenz; David S Friedman; Douglas Gaasterland; et al.
Investigative ophthalmology & visual science 2012;53(8):4468-74. -
3.
2012Gaofeng Wang; William K Scott; Patrice Whitehead; Brenda L Court; Jaclyn L Kovach; Stephen G Schwartz; Anita Agarwal; Sander Dubovy; Jonathan L Haines; Margaret A Pericak-Vance
A novel ARMS2 splice variant is identified in human retina.
Experimental eye research 2012;94(1):187-91. -
4.
2012Janey L Wiggs; Brian L Yaspan; Michael A Hauser; Jae H Kang; R Rand Allingham; Lana M Olson; Wael Abdrabou; Bao J Fan; Dan Y Wang; Wendy Brodeur; et al.
PLoS genetics 2012;8(4):e1002654. -
5.
2011Kylee L Spencer; Lana M Olson; Nathalie Schnetz-Boutaud; Paul Gallins; Gaofeng Wang; William K Scott; Anita Agarwal; Johanna Jakobsdottir; Yvette Conley; Daniel E Weeks; et al.
Investigative ophthalmology & visual science 2011;52(3):1748-54. -
6.
2011Stephan Züchner; Julia Dallman; Rong Wen; Gary Beecham; Adam Naj; Amjad Farooq; Martin A Kohli; Patrice L Whitehead; William Hulme; Ioanna Konidari; et al.
Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa.
American journal of human genetics 2011;88(2):201-6. -
7.
2011Kylee L Spencer; Lana M Olson; Nathalie Schnetz-Boutaud; Paul Gallins; Anita Agarwal; Alessandro Iannaccone; Stephen B Kritchevsky; Melissa Garcia; Michael A Nalls; Anne B Newman; et al.
PloS one 2011;6(3):e17784. -
8.
2010Gaofeng Wang; William K Scott; Jonathan L Haines; Margaret A Pericak-Vance
Genotype at polymorphism rs11200638 and HTRA1 expression level.
Archives of ophthalmology 2010;128(11):1491-3. -
9.
2010Juan A Ayala-Haedo; Paul J Gallins; Patrice L Whitehead; Stephen G Schwartz; Jaclyn L Kovach; Eric A Postel; Anita Agarwal; Gaofeng Wang; Jonathan L Haines; Margaret A Pericak-Vance; et al.
Annals of human genetics 2010;74(3):195-201. -
10.
2010Wei Chen; Dwight Stambolian; Albert O Edwards; Kari E Branham; Mohammad Othman; Johanna Jakobsdottir; Nirubol Tosakulwong; Margaret A Pericak-Vance; Peter A Campochiaro; Michael L Klein; et al.
Proceedings of the National Academy of Sciences of the United States of America 2010;107(16):7401-6. -
11.
2010Digna R Velez Edwards; Paul Gallins; Monica Polk; Juan Ayala-Haedo; Stephen G Schwartz; Jaclyn L Kovach; Kylee Spencer; Gaofeng Wang; Anita Agarwal; Eric A Postel; et al.
Investigative ophthalmology & visual science 2010;51(4):1873-9. -
12.
2010Gaofeng Wang; Kylee L Spencer; William K Scott; Patrice Whitehead; Brenda L Court; Juan Ayala-Haedo; Ping Mayo; Stephen G Schwartz; Jaclyn L Kovach; Paul Gallins; et al.
Analysis of the indel at the ARMS2 3'UTR in age-related macular degeneration.
Human genetics 2010;127(5):595-602. -
13.
2010Martha P Montgomery; Freya Kamel; Margaret A Pericak-Vance; Jonathan L Haines; Eric A Postel; Anita Agarwal; Marie Richards; William K Scott; Silke Schmidt
Overall diet quality and age-related macular degeneration.
Ophthalmic epidemiology 2010;17(1):58-65. -
14.
2009Gaofeng Wang; Kylee L Spencer; Brenda L Court; Lana M Olson; William K Scott; Jonathan L Haines; Margaret A Pericak-Vance
Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria.
Investigative ophthalmology & visual science 2009;50(7):3084-90. -
15.
2008Kelli K Ryckman; Lan Jiang; Chun Li; Jacquelaine Bartlett; Jonathan L Haines; Scott M Williams
A prevalence-based association test for case-control studies.
Genetic epidemiology 2008;32(7):600-5. -
16.
2008Kylee L Spencer; Lana M Olson; Brent M Anderson; Nathalie Schnetz-Boutaud; William K Scott; Paul Gallins; Anita Agarwal; Eric A Postel; Margaret A Pericak-Vance; Jonathan L Haines
C3 R102G polymorphism increases risk of age-related macular degeneration.
Human molecular genetics 2008;17(12):1821-4. -
17.
2008Kylee L Spencer; Michael A Hauser; Lana M Olson; Silke Schmidt; William K Scott; Paul Gallins; Anita Agarwal; Eric A Postel; Margaret A Pericak-Vance; Jonathan L Haines
Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration.
Human molecular genetics 2008;17(7):971-7. -
18.
2008R Keith Shuler; Silke Schmidt; Paul Gallins; Michael A Hauser; William K Scott; Jennifer Caldwell; Anita Agarwal; Jonathan L Haines; Margaret A Pericak-Vance; Eric A Postel
Ophthalmology 2008;115(3):520-4. -
19.
2008R Keith Shuler; Silke Schmidt; Paul Gallins; Michael A Hauser; William K Scott; Jennifer Caldwell; Anita Agarwal; Jonathan L Haines; Margaret A Pericak-Vance; Eric A Postel
American journal of ophthalmology 2008;145(2):303-307. -
20.
2008Jeffrey A Canter; Lana M Olson; Kylee Spencer; Nathalie Schnetz-Boutaud; Brent Anderson; Michael A Hauser; Silke Schmidt; Eric A Postel; Anita Agarwal; Margaret A Pericak-Vance; et al.
PloS one 2008;3(5):e2091. -
21.
2007Kylee L Spencer; Michael A Hauser; Lana M Olson; Nathalie Schnetz-Boutaud; William K Scott; Silke Schmidt; Paul Gallins; Anita Agarwal; Eric A Postel; Margaret A Pericak-Vance; et al.
Investigative ophthalmology & visual science 2007;48(9):4277-83. -
22.
2007Kylee L Spencer; Michael A Hauser; Lana M Olson; Silke Schmidt; William K Scott; Paul Gallins; Anita Agarwal; Eric A Postel; Margaret A Pericak-Vance; Jonathan L Haines
Human molecular genetics 2007;16(16):1986-92. -
23.
2007William K Scott; Silke Schmidt; Michael A Hauser; Paul Gallins; Nathalie Schnetz-Boutaud; Kylee L Spencer; John R Gilbert; Anita Agarwal; Eric A Postel; Jonathan L Haines; et al.
Ophthalmology 2007;114(6):1151-6. -
24.
2007R Keith Shuler; Michael A Hauser; Jennifer Caldwell; Paul Gallins; Silke Schmidt; William K Scott; Anita Agarwal; Jonathan L Haines; Margaret A Pericak-Vance; Eric A Postel
Archives of ophthalmology 2007;125(1):63-7. -
25.
2006Eric A Postel; Anita Agarwal; Jennifer Caldwell; Paul Gallins; Cynthia Toth; Silke Schmidt; William K Scott; Michael A Hauser; Jonathan L Haines; Margaret A Pericak-Vance
Complement factor H increases risk for atrophic age-related macular degeneration.
Ophthalmology 2006;113(9):1504-7. -
26.
2006Silke Schmidt; Michael A Hauser; William K Scott; Eric A Postel; Anita Agarwal; Paul Gallins; Frank Wong; Yu Sarah Chen; Kylee Spencer; Nathalie Schnetz-Boutaud; et al.
American journal of human genetics 2006;78(5):852-64. -
27.
2006Jonathan L Haines; Nathalie Schnetz-Boutaud; Silke Schmidt; William K Scott; Anita Agarwal; Eric A Postel; Lana Olson; Shannon J Kenealy; Michael Hauser; John R Gilbert; et al.
Investigative ophthalmology & visual science 2006;47(1):329-35. -
28.
2005Sheila A Fisher; Goncalo R Abecasis; Beverly M Yashar; Sepideh Zareparsi; Anand Swaroop; Sudha K Iyengar; Barbara E K Klein; Ronald Klein; Kristine E Lee; Jacek Majewski; et al.
Meta-analysis of genome scans of age-related macular degeneration.
Human molecular genetics 2005;14(15):2257-64. -
29.
2005Eric A Postel; Anita Agarwal; Silke Schmidt; Yu-Ti R Fan; William K Scott; John R Gilbert; Jonathan L Haines; Margaret A Pericak-Vance
American journal of ophthalmology 2005;139(5):820-5. -
30.
2005Jonathan L Haines; Michael A Hauser; Silke Schmidt; William K Scott; Lana M Olson; Paul Gallins; Kylee L Spencer; Shu Ying Kwan; Maher Noureddine; John R Gilbert; et al.
Complement factor H variant increases the risk of age-related macular degeneration.
Science (New York, N.Y.) 2005;308(5720):419-21. -
31.
2005Silke Schmidt; Jonathan L Haines; Eric A Postel; Anita Agarwal; Shu Ying Kwan; John R Gilbert; Margaret A Pericak-Vance; William K Scott
Joint effects of smoking history and APOE genotypes in age-related macular degeneration.
Molecular vision 2005;11():941-9. -
32.
2004Silke Schmidt; William K Scott; Eric A Postel; Anita Agarwal; Elizabeth R Hauser; Monica A De La Paz; John R Gilbert; Daniel E Weeks; Michael B Gorin; Jonathan L Haines; et al.
BMC genetics 2004;5():18. -
33.
2004Shannon J Kenealy; Silke Schmidt; Anita Agarwal; Eric A Postel; Monica A De La Paz; Margaret A Pericak-Vance; Jonathan L Haines
Linkage analysis for age-related macular degeneration supports a gene on chromosome 10q26.
Molecular vision 2004;10():57-61. -
34.
2003Silke Schmidt; Eric A Postel; Anita Agarwal; I Coy Allen; Shaune N Walters; Monica A De la Paz; William K Scott; Jonathan L Haines; Margaret A Pericak-Vance; John R Gilbert
Detailed analysis of allelic variation in the ABCA4 gene in age-related maculopathy.
Investigative ophthalmology & visual science 2003;44(7):2868-75. -
35.
2002Silke Schmidt; Caroline Klaver; Ann Saunders; Eric Postel; Monica De La Paz; Anita Agarwal; Kent Small; Nitin Udar; John Ong; Meenal Chalukya; et al.
A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy.
Ophthalmic genetics 2002;23(4):209-23. -
36.
2000S Schmidt; A M Saunders; De La Paz MA; E A Postel; R M Heinis; A Agarwal; W K Scott; J R Gilbert; J G McDowell; A Bazyk; et al.
Molecular vision 2000;6():287-93.
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