Human Molecular Genetics, 2000, Vol. 9, No. 9 1329-1349
© 2000 Oxford University Press
A full genome scan for age-related maculopathy
1Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA, 2Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA, 3Smith-Kettlewell Eye Research Institute, San Francisco, CA 94115, USA, 4Department of Ophthalmology, University of California at Davis, Davis, CA 95816, USA, 5409 Heron Place, Davis, CA 95616, USA and 6Erie Retinal Surgery Inc., Erie, PA 16507, USA
Age-related macular degeneration or age-related maculopathy (ARM) is a major public health issue, as it is the leading cause of irreversible vision loss in the elderly in the Western world. Using three diagnostic models, we have genotyped markers in 16 plausible candidate regions and have carried out a genome-wide screen for ARM susceptibility loci. A panel of 225 ARM families comprising up to 212 affected sib pairs was genotyped for 386 markers. Under our most stringent diagnostic model, the regions with the strongest evidence of linkage were on chromosome 9 near D9S301 and on 10 near D10S1230, with peak multipoint heterogeneity LOD scores (HLOD) of 1.87 and 1.42 and peak GeneHunter-Plus non-parametric LOD scores (GHP LOD) of 1.69 and 1.83. After expanding our initial set of families to 364 ARM families with up to 329 affected sib pairs, the linkage signal on chromosome 9 vanished, while the chromosome 10 signal decreased to a GHP LOD of about 1.0, with a SimIBD P-value of 0.008 under the broadest diagnostic model with marker D10S1236. After error filtration, the GHP LOD increased to 1.27 under our most stringent model and 1.42 under our broadest model, peaking near D10S1236. This peak was seen consistently across all three diagnostic models. Our analyses also excluded up to nine different candidate regions and identified a few other regions of potential linkage, suitable for further studies. Of particular interest was the region on chromosome 5 near D5S1480, where a reasonable candidate gene, glutathione peroxidase 3, resides.
+ To whom correspondence should be addressed. Tel: +1 412 647 2111; Fax: +1 412 647 5880; Email: gorin@vision.eei.upmc.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Leveziel, J. Zerbib, F. Richard, G. Querques, G. Morineau, V. Fremeaux-Bacchi, G. Coscas, G. Soubrane, P. Benlian, and E. H. Souied Genotype-Phenotype Correlations for Exudative Age-Related Macular Degeneration Associated with Homozygous HTRA1 and CFH Genotypes Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3090 - 3094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bok Contributions of Genetics to Our Understanding of Inherited Monogenic Retinal Diseases and Age-Related Macular Degeneration Arch Ophthalmol, February 1, 2007; 125(2): 160 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Iyengar The Quest for Genes Causing Complex Traits in Ocular Medicine: Successes, Interpretations, and Challenges Arch Ophthalmol, January 1, 2007; 125(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Barral, P. J. Francis, D. W. Schultz, M. B. Schain, C. Haynes, J. Majewski, J. Ott, T. Acott, R. G. Weleber, and M. L. Klein Expanded Genome Scan in Extended Families with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5453 - 5459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Baird, F. M. A. Islam, A. J. Richardson, M. Cain, N. Hunt, and R. Guymer Analysis of the Y402H Variant of the Complement Factor H Gene in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4194 - 4198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tuo, B. Ning, C. M. Bojanowski, Z.-N. Lin, R. J. Ross, G. F. Reed, D. Shen, X. Jiao, M. Zhou, E. Y. Chew, et al. Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition PNAS, June 13, 2006; 103(24): 9256 - 9261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rivera, S. A. Fisher, L. G. Fritsche, C. N. Keilhauer, P. Lichtner, T. Meitinger, and B. H.F. Weber Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk Hum. Mol. Genet., November 1, 2005; 14(21): 3227 - 3236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Patel Shared genetic risk factors for obstructive sleep apnea and obesity J Appl Physiol, October 1, 2005; 99(4): 1600 - 1606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Jun, B. E. K. Klein, R. Klein, K. Fox, C. Millard, J. Capriotti, K. Russo, K. E. Lee, R. C. Elston, and S. K. Iyengar Genome-Wide Analyses Demonstrate Novel Loci That Predispose to Drusen Formation Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3081 - 3088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Fisher, G. R. Abecasis, B. M. Yashar, S. Zareparsi, A. Swaroop, S. K. Iyengar, B. E.K. Klein, R. Klein, K. E. Lee, J. Majewski, et al. Meta-analysis of genome scans of age-related macular degeneration Hum. Mol. Genet., August 1, 2005; 14(15): 2257 - 2264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. P. Conley, A. Thalamuthu, J. Jakobsdottir, D. E. Weeks, T. Mah, R. E. Ferrell, and M. B. Gorin Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy Hum. Mol. Genet., July 15, 2005; 14(14): 1991 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zareparsi, M. Buraczynska, K. E.H. Branham, S. Shah, D. Eng, M. Li, H. Pawar, B. M. Yashar, S. E. Moroi, P. R. Lichter, et al. Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration Hum. Mol. Genet., June 1, 2005; 14(11): 1449 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Palmer, S. G. Buxbaum, E. K. Larkin, S. R. Patel, R. C. Elston, P. V. Tishler, and S. Redline Whole Genome Scan for Obstructive Sleep Apnea and Obesity in African-American Families Am. J. Respir. Crit. Care Med., June 15, 2004; 169(12): 1314 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zareparsi, A. C. Reddick, K. E. H. Branham, K. B. Moore, L. Jessup, S. Thoms, M. Smith-Wheelock, B. M. Yashar, and A. Swaroop Association of Apolipoprotein E Alleles with Susceptibility to Age-Related Macular Degeneration in a Large Cohort from a Single Center Invest. Ophthalmol. Vis. Sci., May 1, 2004; 45(5): 1306 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Michaelides, D M Hunt, and A T Moore The genetics of inherited macular dystrophies J. Med. Genet., September 1, 2003; 40(9): 641 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Telmer, A. R. Retchless, A. D. Kinsey, Y. Conley, B. Rigatti, M. B. Gorin, and J. W. Jarvik Detection and Assignment of Mutations and Minihaplotypes in Human DNA Using Peptide Mass Signature Genotyping (PMSG): Application to the Human RDS/Peripherin Gene Genome Res., August 1, 2003; 13(8): 1944 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schmidt, E. A. Postel, A. Agarwal, I. C. Allen Jr, S. N. Walters, M. A. De La Paz, W. K. Scott, J. L. Haines, M. A. Pericak-Vance, and J. R. Gilbert Detailed Analysis of Allelic Variation in the ABCA4 Gene in Age-Related Maculopathy Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 2868 - 2875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Z. Wang, E. Wilson, K. G. Locke, and A. O. Edwards Shape Discrimination in Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., June 1, 2002; 43(6): 2055 - 2062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Weeks, Y. P. Conley, R. E. Ferrell, T. S. Mah, and M. B. Gorin A Tale of Two Genotypes: Consistency between Two High-Throughput Genotyping Centers Genome Res., March 1, 2002; 12(3): 430 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zurdel, U. Finckh, G. Menzer, R. M Nitsch, and G. Richard CST3 genotype associated with exudative age related macular degeneration Br. J. Ophthalmol., February 1, 2002; 86(2): 214 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sharon, S. Blackshaw, C. L. Cepko, and T. P. Dryja Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE) PNAS, December 21, 2001; (2001) 12582799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Kuehn, E. M. Stone, and G. S. Hageman Organization of the Human IMPG2 Gene and Its Evaluation as a Candidate Gene in Age-Related Macular Degeneration and Other Retinal Degenerative Disorders Invest. Ophthalmol. Vis. Sci., December 1, 2001; 42(13): 3123 - 3129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K. Scott, M. A. Nance, R. L. Watts, J. P. Hubble, W. C. Koller, K. Lyons, R. Pahwa, M. B. Stern, A. Colcher, B. C. Hiner, et al. Complete Genomic Screen in Parkinson Disease: Evidence for Multiple Genes JAMA, November 14, 2001; 286(18): 2239 - 2244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Stone, V. C. Sheffield, and G. S. Hageman Molecular genetics of age-related macular degeneration Hum. Mol. Genet., October 1, 2001; 10(20): 2285 - 2292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Gorin The ABCA4 Gene and Age-Related Macular Degeneration: Innocence or Guilt by Association Arch Ophthalmol, May 1, 2001; 119(5): 752 - 753. [Full Text] [PDF]
|
|
|
|
|
|
D. Sharon, S. Blackshaw, C. L. Cepko, and T. P. Dryja Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE) PNAS, January 8, 2002; 99(1): 315 - 320. [Abstract] [Full Text] [PDF]
|
|