Early adult-onset POAG linked to 15q11-13 using ordered subset analysis

R. Rand Allingham, Janey L. Wiggs, Elizabeth R. Hauser, Karen R. Larocque-Abramson, Cecilia Santiago-Turla, Bob Broomer, Elizabeth A. Del Bono, Felicia L. Graham, Jonathan L. Haines, Margaret A Pericak-Vance, Michael A. Hauser

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Abstract

PURPOSE. Primary open-angle glaucoma (POAG) is a complex inherited disorder. It has been demonstrated in other complex disorders that phenotypic heterogeneity may be the result of genetic heterogeneity and that stratification analysis can be used to increase the power of detection. Ordered subset analysis (OSA) is a recently described method that utilizes the variability of phenotypic traits to determine underlying genetic heterogeneity. METHODS. Eighty-six multiplex families with POAG were clinically ascertained for genetic analysis. Age at diagnosis (AAD) was used as a surrogate for age of onset in affected family members. Nine genetic markers within the 15q11-13 interval on chromosome 15 were used for OSA analysis. RESULTS. An 11-cM linkage interval with a peak LOD score of 3.24 centered at the GABRB3 locus (P = 0.013 by permutation test) was identified in a subset of 15 families, which represents 17% of the total dataset (15/86 families). The mean AAD for the affected OSA families was 44.1 ± 9.1 years (SD). The mean AAD for the complementary group was 61.3 ± 10.4 years. African-American and white families were well represented in the OSA subset. CONCLUSIONS. Linkage was identified for POAG to an 11-cM region on chromosome 15, designated GLClI. This result provides further evidence that AAD and other phenotypic traits can be used as stratification variables to identify genes in complex disorders such as POAG and suggests that the 15q11-13 locus is one of the largest genetic contributors to POAG identified to date.

Original languageEnglish
Pages (from-to)2002-2005
Number of pages4
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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Chromosomes, Human, Pair 15
Genetic Heterogeneity
Genetic Markers
Age of Onset
African Americans
Primary Open Angle Glaucoma
Genes
Power (Psychology)
Datasets

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Allingham, R. R., Wiggs, J. L., Hauser, E. R., Larocque-Abramson, K. R., Santiago-Turla, C., Broomer, B., ... Hauser, M. A. (2005). Early adult-onset POAG linked to 15q11-13 using ordered subset analysis. Investigative Ophthalmology and Visual Science, 46(6), 2002-2005. https://doi.org/10.1167/iovs.04-1477

Early adult-onset POAG linked to 15q11-13 using ordered subset analysis. / Allingham, R. Rand; Wiggs, Janey L.; Hauser, Elizabeth R.; Larocque-Abramson, Karen R.; Santiago-Turla, Cecilia; Broomer, Bob; Del Bono, Elizabeth A.; Graham, Felicia L.; Haines, Jonathan L.; Pericak-Vance, Margaret A; Hauser, Michael A.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 6, 01.06.2005, p. 2002-2005.

Research output: Contribution to journalArticle

Allingham, RR, Wiggs, JL, Hauser, ER, Larocque-Abramson, KR, Santiago-Turla, C, Broomer, B, Del Bono, EA, Graham, FL, Haines, JL, Pericak-Vance, MA & Hauser, MA 2005, 'Early adult-onset POAG linked to 15q11-13 using ordered subset analysis', Investigative Ophthalmology and Visual Science, vol. 46, no. 6, pp. 2002-2005. https://doi.org/10.1167/iovs.04-1477
Allingham RR, Wiggs JL, Hauser ER, Larocque-Abramson KR, Santiago-Turla C, Broomer B et al. Early adult-onset POAG linked to 15q11-13 using ordered subset analysis. Investigative Ophthalmology and Visual Science. 2005 Jun 1;46(6):2002-2005. https://doi.org/10.1167/iovs.04-1477
Allingham, R. Rand ; Wiggs, Janey L. ; Hauser, Elizabeth R. ; Larocque-Abramson, Karen R. ; Santiago-Turla, Cecilia ; Broomer, Bob ; Del Bono, Elizabeth A. ; Graham, Felicia L. ; Haines, Jonathan L. ; Pericak-Vance, Margaret A ; Hauser, Michael A. / Early adult-onset POAG linked to 15q11-13 using ordered subset analysis. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 6. pp. 2002-2005.
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abstract = "PURPOSE. Primary open-angle glaucoma (POAG) is a complex inherited disorder. It has been demonstrated in other complex disorders that phenotypic heterogeneity may be the result of genetic heterogeneity and that stratification analysis can be used to increase the power of detection. Ordered subset analysis (OSA) is a recently described method that utilizes the variability of phenotypic traits to determine underlying genetic heterogeneity. METHODS. Eighty-six multiplex families with POAG were clinically ascertained for genetic analysis. Age at diagnosis (AAD) was used as a surrogate for age of onset in affected family members. Nine genetic markers within the 15q11-13 interval on chromosome 15 were used for OSA analysis. RESULTS. An 11-cM linkage interval with a peak LOD score of 3.24 centered at the GABRB3 locus (P = 0.013 by permutation test) was identified in a subset of 15 families, which represents 17{\%} of the total dataset (15/86 families). The mean AAD for the affected OSA families was 44.1 ± 9.1 years (SD). The mean AAD for the complementary group was 61.3 ± 10.4 years. African-American and white families were well represented in the OSA subset. CONCLUSIONS. Linkage was identified for POAG to an 11-cM region on chromosome 15, designated GLClI. This result provides further evidence that AAD and other phenotypic traits can be used as stratification variables to identify genes in complex disorders such as POAG and suggests that the 15q11-13 locus is one of the largest genetic contributors to POAG identified to date.",
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AU - Wiggs, Janey L.

AU - Hauser, Elizabeth R.

AU - Larocque-Abramson, Karen R.

AU - Santiago-Turla, Cecilia

AU - Broomer, Bob

AU - Del Bono, Elizabeth A.

AU - Graham, Felicia L.

AU - Haines, Jonathan L.

AU - Pericak-Vance, Margaret A

AU - Hauser, Michael A.

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N2 - PURPOSE. Primary open-angle glaucoma (POAG) is a complex inherited disorder. It has been demonstrated in other complex disorders that phenotypic heterogeneity may be the result of genetic heterogeneity and that stratification analysis can be used to increase the power of detection. Ordered subset analysis (OSA) is a recently described method that utilizes the variability of phenotypic traits to determine underlying genetic heterogeneity. METHODS. Eighty-six multiplex families with POAG were clinically ascertained for genetic analysis. Age at diagnosis (AAD) was used as a surrogate for age of onset in affected family members. Nine genetic markers within the 15q11-13 interval on chromosome 15 were used for OSA analysis. RESULTS. An 11-cM linkage interval with a peak LOD score of 3.24 centered at the GABRB3 locus (P = 0.013 by permutation test) was identified in a subset of 15 families, which represents 17% of the total dataset (15/86 families). The mean AAD for the affected OSA families was 44.1 ± 9.1 years (SD). The mean AAD for the complementary group was 61.3 ± 10.4 years. African-American and white families were well represented in the OSA subset. CONCLUSIONS. Linkage was identified for POAG to an 11-cM region on chromosome 15, designated GLClI. This result provides further evidence that AAD and other phenotypic traits can be used as stratification variables to identify genes in complex disorders such as POAG and suggests that the 15q11-13 locus is one of the largest genetic contributors to POAG identified to date.

AB - PURPOSE. Primary open-angle glaucoma (POAG) is a complex inherited disorder. It has been demonstrated in other complex disorders that phenotypic heterogeneity may be the result of genetic heterogeneity and that stratification analysis can be used to increase the power of detection. Ordered subset analysis (OSA) is a recently described method that utilizes the variability of phenotypic traits to determine underlying genetic heterogeneity. METHODS. Eighty-six multiplex families with POAG were clinically ascertained for genetic analysis. Age at diagnosis (AAD) was used as a surrogate for age of onset in affected family members. Nine genetic markers within the 15q11-13 interval on chromosome 15 were used for OSA analysis. RESULTS. An 11-cM linkage interval with a peak LOD score of 3.24 centered at the GABRB3 locus (P = 0.013 by permutation test) was identified in a subset of 15 families, which represents 17% of the total dataset (15/86 families). The mean AAD for the affected OSA families was 44.1 ± 9.1 years (SD). The mean AAD for the complementary group was 61.3 ± 10.4 years. African-American and white families were well represented in the OSA subset. CONCLUSIONS. Linkage was identified for POAG to an 11-cM region on chromosome 15, designated GLClI. This result provides further evidence that AAD and other phenotypic traits can be used as stratification variables to identify genes in complex disorders such as POAG and suggests that the 15q11-13 locus is one of the largest genetic contributors to POAG identified to date.

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