BACKGROUND: Although the vertical cup-disc ratio (VCDR) and intraocular pressure (IOP) are important determinants of open angle glaucoma (OAG), it is unclear to what extent the genetic origin of these traits overlap with those of OAG. We evaluated whether the same genes that determine VCDR and IOP also predict OAG. METHODS: Genetic risk scores were constructed from single nucleotide polymorphisms (SNPs) using genome wide association data of 9326 participants from the Rotterdam Study cohorts (mean ± SD age: 64.6 ± 9.1 years). These risk scores were used to calculate the explained variance of VCDR and IOP in an independent cohort (Erasmus Rucphen Family study) consisting of 1646 participants (mean ± SD age: 46.8 ± 14.1 years) and the OAG risk in a subset of the Rotterdam Study cohorts. To evaluate false positive findings, we generated two new variables containing randomly sampled values to serve as a negative control. RESULTS: The explained variance of VCDR increased when increasing the number of SNPs included in the risk score, suggesting a polygenic model. We found no clear evidence for a similar model for IOP, suggesting that a small number of SNPs determine the susceptibility to IOP. The SNPs related to IOP in terms of p values contributed little to VCDR. The risk scores associated with VCDR were also associated significantly with OAG. This suggests a common polygenic background for VCDR and OAG CONCLUSIONS: We found evidence for a polygenic model underlying one of the major traits of OAG, VCDR, and OAG itself. The IOP did not show any evidence for such a model.
BACKGROUND: Although the vertical cup-disc ratio (VCDR) and intraocular pressure (IOP) are important determinants of open angle glaucoma (OAG), it is unclear to what extent the genetic origin of these traits overlap with those of OAG. We evaluated whether the same genes that determine VCDR and IOP also predict OAG. METHODS: Genetic risk scores were constructed from single nucleotide polymorphisms (SNPs) using genome wide association data of 9326 participants from the Rotterdam Study cohorts (mean ± SD age: 64.6 ± 9.1 years). These risk scores were used to calculate the explained variance of VCDR and IOP in an independent cohort (Erasmus Rucphen Family study) consisting of 1646 participants (mean ± SD age: 46.8 ± 14.1 years) and the OAG risk in a subset of the Rotterdam Study cohorts. To evaluate false positive findings, we generated two new variables containing randomly sampled values to serve as a negative control. RESULTS: The explained variance of VCDR increased when increasing the number of SNPs included in the risk score, suggesting a polygenic model. We found no clear evidence for a similar model for IOP, suggesting that a small number of SNPs determine the susceptibility to IOP. The SNPs related to IOP in terms of p values contributed little to VCDR. The risk scores associated with VCDR were also associated significantly with OAG. This suggests a common polygenic background for VCDR and OAG CONCLUSIONS: We found evidence for a polygenic model underlying one of the major traits of OAG, VCDR, and OAG itself. The IOP did not show any evidence for such a model.
Authors: Janey L Wiggs; Michael A Hauser; Wael Abdrabou; Robert Rand Allingham; Donald L Budenz; Elizabeth Delbono; David S Friedman; Jae H Kang; Douglas Gaasterland; Terry Gaasterland; Richard K Lee; Paul R Lichter; Stephanie Loomis; Yutao Liu; Cathy McCarty; Felipe A Medeiros; Sayoko E Moroi; Lana M Olson; Anthony Realini; Julia E Richards; Frank W Rozsa; Joel S Schuman; Kuldev Singh; Joshua D Stein; Douglas Vollrath; Robert N Weinreb; Gadi Wollstein; Brian L Yaspan; Sachiko Yoneyama; Don Zack; Kang Zhang; Margaret Pericak-Vance; Louis R Pasquale; Jonathan L Haines Journal: J Glaucoma Date: 2013-09 Impact factor: 2.503
Authors: Henriët Springelkamp; Adriana I Iglesias; Aniket Mishra; René Höhn; Robert Wojciechowski; Anthony P Khawaja; Abhishek Nag; Ya Xing Wang; Jie Jin Wang; Gabriel Cuellar-Partida; Jane Gibson; Jessica N Cooke Bailey; Eranga N Vithana; Puya Gharahkhani; Thibaud Boutin; Wishal D Ramdas; Tanja Zeller; Robert N Luben; Ekaterina Yonova-Doing; Ananth C Viswanathan; Seyhan Yazar; Angela J Cree; Jonathan L Haines; Jia Yu Koh; Emmanuelle Souzeau; James F Wilson; Najaf Amin; Christian Müller; Cristina Venturini; Lisa S Kearns; Jae Hee Kang; Yih Chung Tham; Tiger Zhou; Elisabeth M van Leeuwen; Stefan Nickels; Paul Sanfilippo; Jiemin Liao; Herma van der Linde; Wanting Zhao; Leonieke M E van Koolwijk; Li Zheng; Fernando Rivadeneira; Mani Baskaran; Sven J van der Lee; Shamira Perera; Paulus T V M de Jong; Ben A Oostra; André G Uitterlinden; Qiao Fan; Albert Hofman; E-Shyong Tai; Johannes R Vingerling; Xueling Sim; Roger C W Wolfs; Yik Ying Teo; Hans G Lemij; Chiea Chuen Khor; Rob Willemsen; Karl J Lackner; Tin Aung; Nomdo M Jansonius; Grant Montgomery; Philipp S Wild; Terri L Young; Kathryn P Burdon; Pirro G Hysi; Louis R Pasquale; Tien Yin Wong; Caroline C W Klaver; Alex W Hewitt; Jost B Jonas; Paul Mitchell; Andrew J Lotery; Paul J Foster; Veronique Vitart; Norbert Pfeiffer; Jamie E Craig; David A Mackey; Christopher J Hammond; Janey L Wiggs; Ching-Yu Cheng; Cornelia M van Duijn; Stuart MacGregor Journal: Hum Mol Genet Date: 2017-01-15 Impact factor: 6.150
Authors: Albert Hofman; Cornelia M van Duijn; Oscar H Franco; M Arfan Ikram; Harry L A Janssen; Caroline C W Klaver; Ernst J Kuipers; Tamar E C Nijsten; Bruno H Ch Stricker; Henning Tiemeier; André G Uitterlinden; Meike W Vernooij; Jacqueline C M Witteman Journal: Eur J Epidemiol Date: 2011-08-30 Impact factor: 8.082