Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis

Holliday, Elizabeth G., Smith, Albert V., Cornes, Belinda K., Buitendijk, Gabrielle H. S., Jensen, Richard A., Sim, Xueling, Aspelund, Thor, Aung, Tin, Baird, Paul N., Boerwinkle, Eric, Cheng, Ching Yu, van Duijn, Cornelia M., Eiriksdottir, Gudny, Gudnason, Vilmundur, Harris, Tamara, Hewitt, Alex W., Inouye, Michael, Jonasson, Fridbert, Klein, Barbara E. K., Launer, Lenore, Li, Xiaohui, Liew, Gerald, Lumley, Thomas, McElduff, Patrick, McKnight, Barbara, Mitchell, Paul, Psaty, Bruce M., Rochtchina, Elena, Rotter, Jerome I., Scott, Rodney J., Tay, Wanting, Taylor, Kent, Teo, Yik Ying, Uitterlinden, Andre G., Viswanathan, Ananth, Xie, Sophia, Vingerling, Johannes R., Klaver, Caroline C. W., Tai, E. Shyong, Siscovick, David, Klein, Ronald, Cotch, Mary Frances, Wong, Tien Y., Attia, John, Wang, Jie Jin and Wellcome Trust Case Control Consortium 2 (2013) Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis. PLoS One, 8 1: . doi:10.1371/journal.pone.0053830

Author Holliday, Elizabeth G.
Smith, Albert V.
Cornes, Belinda K.
Buitendijk, Gabrielle H. S.
Jensen, Richard A.
Sim, Xueling
Aspelund, Thor
Aung, Tin
Baird, Paul N.
Boerwinkle, Eric
Cheng, Ching Yu
van Duijn, Cornelia M.
Eiriksdottir, Gudny
Gudnason, Vilmundur
Harris, Tamara
Hewitt, Alex W.
Inouye, Michael
Jonasson, Fridbert
Klein, Barbara E. K.
Launer, Lenore
Li, Xiaohui
Liew, Gerald
Lumley, Thomas
McElduff, Patrick
McKnight, Barbara
Mitchell, Paul
Psaty, Bruce M.
Rochtchina, Elena
Rotter, Jerome I.
Scott, Rodney J.
Tay, Wanting
Taylor, Kent
Teo, Yik Ying
Uitterlinden, Andre G.
Viswanathan, Ananth
Xie, Sophia
Vingerling, Johannes R.
Klaver, Caroline C. W.
Tai, E. Shyong
Siscovick, David
Klein, Ronald
Cotch, Mary Frances
Wong, Tien Y.
Attia, John
Wang, Jie Jin
Wellcome Trust Case Control Consortium 2
Title Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-01-11
Sub-type Article (original research)
DOI 10.1371/journal.pone.0053830
Open Access Status DOI
Volume 8
Issue 1
Total pages 12
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD). While genome-wide association studies (GWAS) for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes) and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH) (peak P = 1.5×10−31) and age-related maculopathy susceptibility 2 (ARMS2) (P = 4.3×10−24) loci, and suggested Apolipoprotein E (ApoE) polymorphisms (rs2075650; P = 1.1×10−6) associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9×10−6) and upstream of GLI2 (rs6721654; P = 6.5×10−6), encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR) gene (rs621313; P = 3.5×10−6), involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Article number e53830

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 56 times in Thomson Reuters Web of Science Article | Citations
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