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Macular Degeneration Research - Completed Award

Photo Pending

Josephine Hoh, Ph.D.

Yale University
New Haven, CT

Title: AMD Beyond Complement and Serine Protease Pathways
Non-Technical Title: A study to examine genetic factors leading to AMD

Duration: April 1, 2007 - March 31, 2010
Award Type: Standard
Award Amount: $100,000


Summary:

This study will characterize two new genetic risk factors related to wet and dry AMD

Details:


Age-related macular degeneration (AMD) has a complex etiology and is broadly classified as either dry or wet. The dry form is more common, accounting for approximately 90% of patients, and does not typically result in blindness. About 10% of patients have the wet form, in which central vision will be destroyed. We have identified two major genetic factors predisposing some individuals to the more aggressive wet form of AMD and others to the slowly progressing dry type. Together with the new risk factors we will discover, it will be possible to detect who is at increased risk and allow those affected to take preventive measures.

Publications:

Ennis, S, Goverdhan S, Cree A.J., Hoh J, Collins A, Lotery AJ. (2007) Fine scale Linkage Disequilibrium mapping of Age Related Macular Degeneration in the Complement Factor H gene region. Br. J. Ophthalmol. 91(7):966-970. Epub 2007 Feb 21 PubMed Icon Google Scholar Icon

Yoshida, T., DeWan, A., Zhang, H., Sakamoto, R., Okamoto, H., Minami, M., Obazawa, M., Mizota, A., Tanaka, M, Saito, Y, Takagi, I, Hoh, J., Iwata, T. (2007) HTRA1 Promoter Polymorphism Predisposes Japanese to AMD. Mol. Vis. Apr 4;13:545-548. PubMed Icon Google Scholar Icon

Dewan A, Bracken M, Hoh J. (2007) Two genetic pathways for age-related macular degeneration. Curr. Opin. Genet. Dev. 17(3):228-233. Epub 2007 Apr 27. PubMed Icon Google Scholar Icon

NCI-NHGRI Working Group on Replication in Association Studies, Chanock, S.J., Manolio, T., Boehnke, M., Boerwinkle, E., Hunter, D.J., Thomas, G., Hirschhorn, J.N., Abecasis, G., Altshuler, D., Bailey-Wilson, J.E., Brooks, L.D., Cardon, L.R., Daly, M., Donnelly, P., Fraumeni, J.F. Jr, Freimer, N.B., Gerhard, D.S., Gunter, C., Guttmacher, A.E., Guyer, M.S., Harris, E.L., Hoh, J., Hoover, R., Kong, C.A., Merikangas, K.R., Morton, C.C., Palmer, L.J., Phimister, E.G., Rice, J.P., Roberts, J., Rotimi, C., Tucker, M.A., Vogan, K.J., Wacholder, S., Wijsman, E.M., Winn, D.M., Collins, F.S. (2007) Replicating genotype-phenotype associations. Nature. 447(7145):655-660. PubMed Icon Google Scholar Icon

DeWan, A., Klein, R.J., Hoh, J. (2007) Linkage disequilibrium mapping for complex disease genes.Methods Mol Biol. 17(3):228-233. Epub 2007 Apr 27. PubMed Icon Google Scholar Icon

[Book Chapter] Hoh, J. (2007) Age-related macular degeneration. In: Encyclopedia of Global Health. Gibbs D, Yang Z, Constantine R, Ma X, Camp NJ, Yang X, Chen H, Jorgenson A, Hau V, Dewan A, Zeng J, Harmon J, Buehler J, Brand JM, Hoh J, Cameron DJ, Dixit M, Tong Z, Zhang K. Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration. Vision Res. 2008 Feb;48(5):685-9. Epub 2008 Jan 22. PubMed Icon Google Scholar Icon

Zhang H, Morrison MA, Dewan A, Adams S, Andreoli M, Huynh N, Regan M, Brown A, Miller JW, Kim IK, Hoh J, Deangelis MM. The NEI/NCBI dbGAP database: genotypes and haplotypes that may specifically predispose to risk of neovascular agerelated macular degeneration. BMC Med Genet. 2008 Jun 9;9:51. PubMed Icon Google Scholar Icon

Tam PO, Ng TK, Liu DT, Chan WM, Chiang SW, Chen LJ, DeWan A, Hoh J, Lam DS, Pang CP. HTRA1 variants in exudative age-related macular degeneration and interactions with smoking and CFH. Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2357-65. PubMed Icon Google Scholar Icon

Ormsby RJ, Ranganathan S, Tong JC, Griggs KM, Dimasi DP, Hewitt AW, Burdon KP, Craig JE, Hoh J, Gordon DL. Functional and structural implications of the complement factor H Y402H polymorphism associated with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2008 May;49(5):1763- 70. PubMed Icon Google Scholar Icon

Francis PJ, Zhang H, Dewan A, Hoh J, Klein ML. Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population. Mol Vis. 2008 Aug 4;14:1395-400. PubMed Icon Google Scholar Icon

Yan T, Yang YN, Cheng X, DeAngelis MM, Hoh J, Zhang H. Genotypic association analysis using discordant-relative-pairs. Ann Hum Genet. 2009 Jan;73(1):84-94. Epub 2008 Nov 21. PubMed Icon Google Scholar Icon

Chowers I, Meir T, Lederman M, Goldenberg-Cohen N, Cohen Y, Banin E, Averbukh E, Hemo I, Pollack A, Axer-Siegel R, Weinstein O, Hoh J, Zack DJ, Galbinur T. Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to photodynamic therapy in neovascular age-related macular degeneration in populations from Israel. Mol Vis. 2008;14:2263-71. PubMed Icon Google Scholar Icon

SanGiovanni JP, Arking DE, Iyengar SK, Elashoff M, Clemons TE, Reed GF, Henning AK, Sivakumaran TA, Xu X, DeWan A, Agron E, Rochtchina E, Sue CM, Wang JJ, Mitchell P, Hoh J, Francis PJ, Klein ML, Chew EY, Chakravarti A. Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration. PLoS One. 2009;4(5):e5508. PubMed Icon Google Scholar Icon

Mason AB, Hoh J. CCR3: Shedding new light on a dark problem? J Mol Cell Biol. 2009 Oct;1(1):17-9. PubMed Icon Google Scholar Icon

Harris CR, Dewan A, Zupnick A, Normart R, Gabriel A, Prives C, Levine AJ, Hoh J. 53 responsive elements in human retrotransposons. Oncogene. 2009 Nov 5;28(44):3857-65. PubMed Icon Google Scholar Icon

Jiao X, Yang Z, Yang X, Chen Y, Tong Z, Zhao C, Zeng J, Chen H, Gibbs D, Sun X, Li B, Wakins WS, Meyer C, Wang X, Kasuga D, Bedell M, Pearson E, Weinreb RN, Leske MC, Hennis A, DeWan A, Nemesure B, Jorde LB, Hoh J, Hejtmancik JF, Zhang K. Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17105-10. Epub 2009 Sep 24. PubMed Icon Google Scholar Icon

Wu C, Zhang H, Liu X, DeWan A, Dubrow R, Ying, Z, Yang Y, Hoh J. Detecting interactions in genome-wide association studies. Statistics and Its Interface. 2009. 2(2): 161-170.27 [PMID:][link not available] Zhang K, Jiao X, Chen Y, Yang Z, Hennis A, Nemesure B, Hoh J, Hejtmancik JF, Response to Mabuchi et al: Differential associations of genetic variations and glaucoma in ethnically diverse populations. Proc Natl Acad Sci U S A. Hoh J, Ott J. 'Scan Statistics in Genome-Wide Scan for Complex Trait Loci' in Scan Statistics, Publisher: Springer, 2009 Hoh J. 'Genetics of Age-related Macular Degeneration' in Macular Surgery, Second Edition. Editors: Hugo Quiroz- Mercado, Yasuo Tano, William F. Mieler, Virgil Alfara, Peter E. Liggett & John B. Kerrison. Lippencott Williams & Wilkins. In Press.