A full genome scan for age-related maculopathy

Daniel E. Weeks, Yvette P. Conley, Tammy S. Mah, T. Otis Paul, Lawrence S Morse, Julilani Ngo-Chang, J. P. Dailey, Robert E. Ferrell, Michael B. Gorin

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

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 Gene-Hunter-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 SimlBD 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.

Original languageEnglish (US)
Pages (from-to)1329-1349
Number of pages21
JournalHuman Molecular Genetics
Volume9
Issue number9
StatePublished - May 22 2000

Fingerprint

Macular Degeneration
Genome
Chromosomes, Human, Pair 9
Genes
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 5
Western World
Glutathione Peroxidase
Public Health

ASJC Scopus subject areas

  • Genetics

Cite this

Weeks, D. E., Conley, Y. P., Mah, T. S., Paul, T. O., Morse, L. S., Ngo-Chang, J., ... Gorin, M. B. (2000). A full genome scan for age-related maculopathy. Human Molecular Genetics, 9(9), 1329-1349.

A full genome scan for age-related maculopathy. / Weeks, Daniel E.; Conley, Yvette P.; Mah, Tammy S.; Paul, T. Otis; Morse, Lawrence S; Ngo-Chang, Julilani; Dailey, J. P.; Ferrell, Robert E.; Gorin, Michael B.

In: Human Molecular Genetics, Vol. 9, No. 9, 22.05.2000, p. 1329-1349.

Research output: Contribution to journalArticle

Weeks, DE, Conley, YP, Mah, TS, Paul, TO, Morse, LS, Ngo-Chang, J, Dailey, JP, Ferrell, RE & Gorin, MB 2000, 'A full genome scan for age-related maculopathy', Human Molecular Genetics, vol. 9, no. 9, pp. 1329-1349.
Weeks DE, Conley YP, Mah TS, Paul TO, Morse LS, Ngo-Chang J et al. A full genome scan for age-related maculopathy. Human Molecular Genetics. 2000 May 22;9(9):1329-1349.
Weeks, Daniel E. ; Conley, Yvette P. ; Mah, Tammy S. ; Paul, T. Otis ; Morse, Lawrence S ; Ngo-Chang, Julilani ; Dailey, J. P. ; Ferrell, Robert E. ; Gorin, Michael B. / A full genome scan for age-related maculopathy. In: Human Molecular Genetics. 2000 ; Vol. 9, No. 9. pp. 1329-1349.
@article{2b4ecea164564bf79cce841f498c2174,
title = "A full genome scan for age-related maculopathy",
abstract = "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 Gene-Hunter-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 SimlBD 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.",
author = "Weeks, {Daniel E.} and Conley, {Yvette P.} and Mah, {Tammy S.} and Paul, {T. Otis} and Morse, {Lawrence S} and Julilani Ngo-Chang and Dailey, {J. P.} and Ferrell, {Robert E.} and Gorin, {Michael B.}",
year = "2000",
month = "5",
day = "22",
language = "English (US)",
volume = "9",
pages = "1329--1349",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - A full genome scan for age-related maculopathy

AU - Weeks, Daniel E.

AU - Conley, Yvette P.

AU - Mah, Tammy S.

AU - Paul, T. Otis

AU - Morse, Lawrence S

AU - Ngo-Chang, Julilani

AU - Dailey, J. P.

AU - Ferrell, Robert E.

AU - Gorin, Michael B.

PY - 2000/5/22

Y1 - 2000/5/22

N2 - 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 Gene-Hunter-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 SimlBD 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.

AB - 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 Gene-Hunter-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 SimlBD 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.

UR - http://www.scopus.com/inward/record.url?scp=0034702032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034702032&partnerID=8YFLogxK

M3 - Article

VL - 9

SP - 1329

EP - 1349

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 9

ER -