May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Genomic Screen and Follow-up Analysis on AMD Multiplex Families
Author Affiliations & Notes
  • S. Schmidt
    Ctr for Human Genetics, Duke Univ Med Ctr, Durham, NC, United States
  • W.K. Scott
    Ctr for Human Genetics, Duke Univ Med Ctr, Durham, NC, United States
  • E.A. Postel
    Duke Eye Center, Durham, NC, United States
  • A. Agarwal
    Dept Ophthalmology, Vanderbilt Univ Med Ctr, Nashville, TN, United States
  • M. De La Paz
    Dept Ophthalmology, Vanderbilt Univ Med Ctr, Nashville, TN, United States
  • J.R. Gilbert
    Dept Ophthalmology, Vanderbilt Univ Med Ctr, Nashville, TN, United States
  • D.E. Weeks
    Dept Human Genetics, Univ Pittsburgh Grad School of Public Health, Pittsburgh, PA, United States
  • J.L. Haines
    Program of Human Genetics, Vanderbilt Univ Med Ctr, Nashville, TN, United States
  • M.B. Gorin
    Dept Ophthalmology, Univ Pittsburgh School of Medicine, Pittsburgh, PA, United States
  • M.A. Pericak-Vance
    Dept Ophthalmology, Univ Pittsburgh School of Medicine, Pittsburgh, PA, United States
  • Footnotes
    Commercial Relationships  S. Schmidt, None; W.K. Scott, None; E.A. Postel, None; A. Agarwal, None; M. De La Paz, None; J.R. Gilbert, None; D.E. Weeks, None; J.L. Haines, None; M.B. Gorin, None; M.A. Pericak-Vance, None.
  • Footnotes
    Support  NIH Grant EY 12118
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 2016. doi:
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      S. Schmidt, W.K. Scott, E.A. Postel, A. Agarwal, M. De La Paz, J.R. Gilbert, D.E. Weeks, J.L. Haines, M.B. Gorin, M.A. Pericak-Vance; Genomic Screen and Follow-up Analysis on AMD Multiplex Families . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2016.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: To identify genomic regions harboring susceptibility genes for AMD from a whole genome screen on 62 multiplex families and follow-up analysis of an additional 26 families, taking into account genotypes at the apolipoprotein E (APOE) locus and information about the smoking status of affected individuals. Methods: 392 microsatellite markers were genotyped on 224 affected sib-pair AMD families at the Center for Inherited Disease Research (CIDR). They included 62 families from Duke and Vanderbilt University Medical Center with a total of 114 affected sib pairs. Twopoint and multipoint linkage analysis methods were applied to this data set. In the genetic analysis of complex disorders, it is important to take into account information about known or suspected genetic or environmental risk factors for AMD in an effort to identify more homogeneous subgroups of families. Smoking and the APOE gene are currently the most consistently identified factors influencing the risk of AMD. To incorporate information about APOE genotypes and smoking status, we conducted stratified analyses of families in whom all affected individuals were lacking the APOE-4 allele, and of those in whom 2+ affected siblings were smokers. We have begun to follow up our initial analysis by genotyping peak markers in an additional 26 multiplex families. Results: We obtained parametric twopoint HLOD scores greater than 1.5 in two chromosomal regions: Chromosome (chr) 9q21 near marker D9S301 (HLOD=1.77) and chr 10p14 near D10S189 (HLOD=2.28). Multipoint analysis with SIBLINK gave a nonparametric MLS of 1.97 in the chr 16p13 region (near D16S2616). Most of the evidence for linkage to D9S301 came from affected sib pairs (ASPs) lacking APOE-4 alleles (HLOD=2.33), and this subset also improved the linkage signal on chr 16p13. A linkage signal (HLOD>1.0) at a more distal marker on chr 9q (D9S934) was contributed primarily by ASPs who reported a smoking history. Discussion: We have identified several linkage regions worthy of follow-up analysis. Our results illustrate the importance of accounting for known or suspected risk factors for AMD, since more homogeneous subgroups of families may improve existing linkage signals.

Keywords: age-related macular degeneration • gene mapping • genetics 
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