Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach

Alexandra C. Silveira; Margaux A. Morrison; Fei Ji; Haiyan Xu; James B. Reinecke; Scott M. Adams; Trevor M. Arneberg; Maria Janssian; Joo Eun Lee; Yang Yuan; Debra A. Schaumberg; Maria G. Kotoula; Evangeline E. Tsironi; Aristoteles N. Tsiloulis; Dimitrios Z. Chatzoulis; Joan W. Miller; Ivana K. Kim; Gregory S. Hageman; Lindsay A. Farrer; Neena B. Haider; Margaret M. DeAngelis

doi:10.1016/j.visres.2009.09.016

Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach

Alexandra C. Silveira
, Margaux A. Morrison
, Fei Ji
, Haiyan Xu
, James B. Reinecke
, Scott M. Adams
, Trevor M. Arneberg
, Maria Janssian
, Joo Eun Lee
, Yang Yuan
, Debra A. Schaumberg
, Maria G. Kotoula
, Evangeline E. Tsironi
, Aristoteles N. Tsiloulis
, Dimitrios Z. Chatzoulis
, Joan W. Miller
, Ivana K. Kim
, Gregory S. Hageman
, Lindsay A. Farrer
, Neena B. Haider

Margaret M. DeAngelis

Department of Ophthalmology

Massachusetts Eye and Ear
Rockefeller University
University of Nebraska Medical Center
Brigham and Women’s Hospital
University of Thessaly
University of Iowa
Boston University

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology.

Original language	English
Pages (from-to)	698-715
Number of pages	18
Journal	Vision Research
Volume	50
Issue number	7
DOIs	https://doi.org/10.1016/j.visres.2009.09.016
State	Published - Mar 2010

Keywords

Haplotypes
Linkage
Microarray
Neovascularization
RORA
Single nucleotide polymorphisms

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Silveira, A. C., Morrison, M. A., Ji, F., Xu, H., Reinecke, J. B., Adams, S. M., Arneberg, T. M., Janssian, M., Lee, J. E., Yuan, Y., Schaumberg, D. A., Kotoula, M. G., Tsironi, E. E., Tsiloulis, A. N., Chatzoulis, D. Z., Miller, J. W., Kim, I. K., Hageman, G. S., Farrer, L. A., ... DeAngelis, M. M. (2010). Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach. Vision Research, 50(7), 698-715. https://doi.org/10.1016/j.visres.2009.09.016

@article{fc394b5f54d744eab1bd132e5d2b650d,

title = "Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach",

abstract = "To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology.",

keywords = "Haplotypes, Linkage, Microarray, Neovascularization, RORA, Single nucleotide polymorphisms",

author = "Silveira, \{Alexandra C.\} and Morrison, \{Margaux A.\} and Fei Ji and Haiyan Xu and Reinecke, \{James B.\} and Adams, \{Scott M.\} and Arneberg, \{Trevor M.\} and Maria Janssian and Lee, \{Joo Eun\} and Yang Yuan and Schaumberg, \{Debra A.\} and Kotoula, \{Maria G.\} and Tsironi, \{Evangeline E.\} and Tsiloulis, \{Aristoteles N.\} and Chatzoulis, \{Dimitrios Z.\} and Miller, \{Joan W.\} and Kim, \{Ivana K.\} and Hageman, \{Gregory S.\} and Farrer, \{Lindsay A.\} and Haider, \{Neena B.\} and DeAngelis, \{Margaret M.\}",

year = "2010",

month = mar,

doi = "10.1016/j.visres.2009.09.016",

language = "English",

volume = "50",

pages = "698--715",

journal = "Vision Research",

issn = "0042-6989",

publisher = "Elsevier Ltd",

number = "7",

}

Silveira, AC, Morrison, MA, Ji, F, Xu, H, Reinecke, JB, Adams, SM, Arneberg, TM, Janssian, M, Lee, JE, Yuan, Y, Schaumberg, DA, Kotoula, MG, Tsironi, EE, Tsiloulis, AN, Chatzoulis, DZ, Miller, JW, Kim, IK, Hageman, GS, Farrer, LA, Haider, NB & DeAngelis, MM 2010, 'Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach', Vision Research, vol. 50, no. 7, pp. 698-715. https://doi.org/10.1016/j.visres.2009.09.016

Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach. / Silveira, Alexandra C.; Morrison, Margaux A.; Ji, Fei et al.
In: Vision Research, Vol. 50, No. 7, 03.2010, p. 698-715.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD

T2 - A systems biology based approach

AU - Silveira, Alexandra C.

AU - Morrison, Margaux A.

AU - Ji, Fei

AU - Xu, Haiyan

AU - Reinecke, James B.

AU - Adams, Scott M.

AU - Arneberg, Trevor M.

AU - Janssian, Maria

AU - Lee, Joo Eun

AU - Yuan, Yang

AU - Schaumberg, Debra A.

AU - Kotoula, Maria G.

AU - Tsironi, Evangeline E.

AU - Tsiloulis, Aristoteles N.

AU - Chatzoulis, Dimitrios Z.

AU - Miller, Joan W.

AU - Kim, Ivana K.

AU - Hageman, Gregory S.

AU - Farrer, Lindsay A.

AU - Haider, Neena B.

AU - DeAngelis, Margaret M.

PY - 2010/3

Y1 - 2010/3

N2 - To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology.

AB - To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology.

KW - Haplotypes

KW - Linkage

KW - Microarray

KW - Neovascularization

KW - RORA

KW - Single nucleotide polymorphisms

UR - https://www.scopus.com/pages/publications/77950542695

U2 - 10.1016/j.visres.2009.09.016

DO - 10.1016/j.visres.2009.09.016

M3 - Article

C2 - 19786043

AN - SCOPUS:77950542695

SN - 0042-6989

VL - 50

SP - 698

EP - 715

JO - Vision Research

JF - Vision Research

IS - 7

ER -

Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach

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Keywords

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