Linkage and Association Studies for Macular Degeneration
Principal Investigator
Co-Principal Investigator
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University of Pittsburgh
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University of Pittsburgh
Project Goals
We are investigating the genetic variations that contribute to ARM so that we can eventually understand the causes of this complex condition. We study the genetic variations that are shared among ARM-affected individuals within families as well as compare the frequencies of genetic variations in ARM-affected individuals with those in unaffected persons who are matched in age, gender, and exposures.
Project Summary
Age-related macular degeneration (ARM) is a major cause of vision loss in the elderly. It is thought that smoking and diet may contribute to the risk of developing the condition but it is clear that heredity plays a major role. Variations in two genes, CFH and PLEKHA1/LOC387715, have been found to strongly contribute to the risk of developing ARM, but there are additional genes that probably influence a person's chances of having this condition and how they will progress to vision loss. We are investigating the genetic variations that contribute to ARM so that we can eventually understand the causes of this complex condition. We study the genetic variations that are shared among ARM-affected individuals within families as well as compare the frequencies of genetic variations in ARM-affected individuals with those in unaffected persons who are matched in age, gender, and exposures. Our long-term goals are to develop new preventive therapies that can slow or halt the development of this disease and to be able to provide these treatments to those who are at greatest risk before they experience vision-threatening changes.
Publications
Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, Tosakulwong N, Pericak-Vance MA, Campochiaro PA, Klein ML, Tan PL, Conley YP, Kanda A, Kopplin L, Li Y, Augustaitis KJ, Karoukis AJ, Scott WK, Agarwal A, Kovach JL, Schwartz SG, Postel EA, Brooks M, Baratz KH, Brown WL; Complications of Age-Related Macular Degeneration Prevention Trial Research Group, Brucker AJ, Orlin A, Brown G, Ho A, Regillo C, Donoso L, Tian L, Kaderli B, Hadley D, Hagstrom SA, Peachey NS, Klein R, Klein BE, Gotoh N, Yamashiro K, Ferris Iii F, Fagerness JA, Reynolds R, Farrer LA, Kim IK, Miller JW, Corton M, Carracedo A, Sanchez-Salorio M, Pugh EW, Doheny KF, Brion M, Deangelis MM, Weeks DE, Zack DJ, Chew EY, Heckenlively JR, Yoshimura N, Iyengar SK, Francis PJ, Katsanis N, Seddon JM, Haines JL, Gorin MB, Abecasis GR, Swaroop A. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7401-6. Epub 2010 Apr 12. (PMID:20385819)[link not available] Jakobsdottir J, Gorin MB, Conley YP, Ferrell RE, Weeks DE. Interpretation of genetic association studies: markers with replicated highly significant odds ratios may be poor classifiers. PLoS Genet. 2009 Feb;5(2):e1000337 Epub 2009 Feb 6. (PMID:19197355)[link not available] This paper evaluated our current knowledge of the genetic variants that are associated with the risk of AMD and showed that, at this time, using these variants to test the general population for the future risk of developing AMD is not warranted and would lead to a large number of individuals being incorrectly classified. Jakobsdottir J, Conley YP, Weeks DE, Ferrell RE, Gorin MB. C2 and CFB genes in age-related maculopathy and joint action with CFH and LOC387715 genes. PLoS ONE. 2008 May 21;3(5):e2199. (PMID:18493315)[link not available] MB Gorin, J Jakobsdottir, YP Conley, RE Ferrell, W Chen, A Swaroop, GR Abecasis, Ortube MC and DE Weeks. Further Explorations in the Genetics of Age-related Maculopathy (ARM) 2009 ARVO (Ft Lauderdale, FL) This abstract describes the results of our screening for additional genes that might be associated with AMD risk. G.J. McKay, AMD APOE Consortia. Pooled Data Analysis of Apoe Risk in AMD 2010 ARVO (Ft Lauderdale, FL) This study confirmed the association of ApoE variants with AMD and has provided the best available estimate as to the magnitude of the effect of ApoE variants on the development of advanced AMD.
First published on: June 11, 2008
Last modified on: November 19, 2024