PURPOSE: Central corneal thickness (CCT) is a clinically important risk factor for primary open-angle glaucoma and keratoconus. Genetic factors controlling CCT in Latinos, the most populous minority population in the United States, are unclear. Here we describe the first genome-wide association study (GWAS) report of CCT in Latinos. METHODS: We performed a GWAS for CCT on 1768 Latinos recruited in the Los Angeles Latino Eye Study (LALES) using Illumina's HumanOmniExpress BeadChip (∼730K markers). To discover additional associated single-nucleotide polymorphisms (SNPs), we imputed SNPs based on the 1000 Genomes Project reference panels. All subjects were 40 years of age and older. We used linear regression with adjustment for age, sex, and principal components of genetic ancestry. RESULTS: we replicated the involvement of several previously reported loci, SUCH AS RXRA-COL5A1, FOXO1, and ZNF469, for CCT in Latinos (P 0.002). moreover, we discovered novel SNPS, RS3118515, RS943423, RS3118594, AND RS3132307, THAT REACHED GWAS SIGNIFICANCE (P 5 10(8)) in the uncharacterized LOC100506532 (GENE TYPE: miscRNA) for CCT in Latinos. By conditional analysis, we demonstrate that rs3118515 in this gene is responsible for the GWAS signal in the chromosome 9 RXRA-COL5A1 region in Latinos. Moreover, multiple sources of ENCODE evidence suggest that rs3118515 is in a regulatory region. Reverse-transcription PCR products indicated that transcripts of LOC100506532 surrounding rs3118515 were expressed in human corneas. CONCLUSIONS: We discovered novel SNPs for CCT in Latinos and provided the first reported evidence of the corneal expression of LOC100506532. These results help to further increase our understanding of the genetic architecture of CCT.
PURPOSE:Central corneal thickness (CCT) is a clinically important risk factor for primary open-angle glaucoma and keratoconus. Genetic factors controlling CCT in Latinos, the most populous minority population in the United States, are unclear. Here we describe the first genome-wide association study (GWAS) report of CCT in Latinos. METHODS: We performed a GWAS for CCT on 1768 Latinos recruited in the Los Angeles Latino Eye Study (LALES) using Illumina's HumanOmniExpress BeadChip (∼730K markers). To discover additional associated single-nucleotide polymorphisms (SNPs), we imputed SNPs based on the 1000 Genomes Project reference panels. All subjects were 40 years of age and older. We used linear regression with adjustment for age, sex, and principal components of genetic ancestry. RESULTS: we replicated the involvement of several previously reported loci, SUCH AS RXRA-COL5A1, FOXO1, and ZNF469, for CCT in Latinos (P 0.002). moreover, we discovered novel SNPS, RS3118515, RS943423, RS3118594, AND RS3132307, THAT REACHED GWAS SIGNIFICANCE (P 5 10(8)) in the uncharacterized LOC100506532 (GENE TYPE: miscRNA) for CCT in Latinos. By conditional analysis, we demonstrate that rs3118515 in this gene is responsible for the GWAS signal in the chromosome 9 RXRA-COL5A1 region in Latinos. Moreover, multiple sources of ENCODE evidence suggest that rs3118515 is in a regulatory region. Reverse-transcription PCR products indicated that transcripts of LOC100506532 surrounding rs3118515 were expressed in human corneas. CONCLUSIONS: We discovered novel SNPs for CCT in Latinos and provided the first reported evidence of the corneal expression of LOC100506532. These results help to further increase our understanding of the genetic architecture of CCT.
Authors: Xianyun Mao; Abigail W Bigham; Rui Mei; Gerardo Gutierrez; Ken M Weiss; Tom D Brutsaert; Fabiola Leon-Velarde; Lorna G Moore; Enrique Vargas; Paul M McKeigue; Mark D Shriver; Esteban J Parra Journal: Am J Hum Genet Date: 2007-04-20 Impact factor: 11.025
Authors: Yi Lu; Veronique Vitart; Kathryn P Burdon; Chiea Chuen Khor; Yelena Bykhovskaya; Alireza Mirshahi; Alex W Hewitt; Demelza Koehn; Pirro G Hysi; Wishal D Ramdas; Tanja Zeller; Eranga N Vithana; Belinda K Cornes; Wan-Ting Tay; E Shyong Tai; Ching-Yu Cheng; Jianjun Liu; Jia-Nee Foo; Seang Mei Saw; Gudmar Thorleifsson; Kari Stefansson; David P Dimasi; Richard A Mills; Jenny Mountain; Wei Ang; René Hoehn; Virginie J M Verhoeven; Franz Grus; Roger Wolfs; Raphaële Castagne; Karl J Lackner; Henriët Springelkamp; Jian Yang; Fridbert Jonasson; Dexter Y L Leung; Li J Chen; Clement C Y Tham; Igor Rudan; Zoran Vatavuk; Caroline Hayward; Jane Gibson; Angela J Cree; Alex MacLeod; Sarah Ennis; Ozren Polasek; Harry Campbell; James F Wilson; Ananth C Viswanathan; Brian Fleck; Xiaohui Li; David Siscovick; Kent D Taylor; Jerome I Rotter; Seyhan Yazar; Megan Ulmer; Jun Li; Brian L Yaspan; Ayse B Ozel; Julia E Richards; Sayoko E Moroi; Jonathan L Haines; Jae H Kang; Louis R Pasquale; R Rand Allingham; Allison Ashley-Koch; Paul Mitchell; Jie Jin Wang; Alan F Wright; Craig Pennell; Timothy D Spector; Terri L Young; Caroline C W Klaver; Nicholas G Martin; Grant W Montgomery; Michael G Anderson; Tin Aung; Colin E Willoughby; Janey L Wiggs; Chi P Pang; Unnur Thorsteinsdottir; Andrew J Lotery; Christopher J Hammond; Cornelia M van Duijn; Michael A Hauser; Yaron S Rabinowitz; Norbert Pfeiffer; David A Mackey; Jamie E Craig; Stuart Macgregor; Tien Y Wong Journal: Nat Genet Date: 2013-01-06 Impact factor: 38.330
Authors: Veronique Vitart; Goran Bencić; Caroline Hayward; Jelena Skunca Herman; Jennifer Huffman; Susan Campbell; Kajo Bućan; Pau Navarro; Grgo Gunjaca; Josipa Marin; Lina Zgaga; Ivana Kolcić; Ozren Polasek; Mirna Kirin; Nicholas D Hastie; James F Wilson; Igor Rudan; Harry Campbell; Zoran Vatavuk; Brian Fleck; Alan Wright Journal: Hum Mol Genet Date: 2010-08-18 Impact factor: 6.150
Authors: Rodrigo J Torres; Emily Jones; Beth Edmunds; Thomas Becker; George A Cioffi; Steven L Mansberger Journal: Am J Ophthalmol Date: 2008-07-30 Impact factor: 5.258
Authors: Matthew P Conomos; Cecelia A Laurie; Adrienne M Stilp; Stephanie M Gogarten; Caitlin P McHugh; Sarah C Nelson; Tamar Sofer; Lindsay Fernández-Rhodes; Anne E Justice; Mariaelisa Graff; Kristin L Young; Amanda A Seyerle; Christy L Avery; Kent D Taylor; Jerome I Rotter; Gregory A Talavera; Martha L Daviglus; Sylvia Wassertheil-Smoller; Neil Schneiderman; Gerardo Heiss; Robert C Kaplan; Nora Franceschini; Alex P Reiner; John R Shaffer; R Graham Barr; Kathleen F Kerr; Sharon R Browning; Brian L Browning; Bruce S Weir; M Larissa Avilés-Santa; George J Papanicolaou; Thomas Lumley; Adam A Szpiro; Kari E North; Ken Rice; Timothy A Thornton; Cathy C Laurie Journal: Am J Hum Genet Date: 2016-01-07 Impact factor: 11.025
Authors: Shinwu Jeong; Nitin Patel; Christopher K Edlund; Jaana Hartiala; Dennis J Hazelett; Tatsuo Itakura; Pei-Chang Wu; Robert L Avery; Janet L Davis; Harry W Flynn; Geeta Lalwani; Carmen A Puliafito; Hussein Wafapoor; Minako Hijikata; Naoto Keicho; Xiaoyi Gao; Pablo Argüeso; Hooman Allayee; Gerhard A Coetzee; Mathew T Pletcher; David V Conti; Stephen G Schwartz; Alexander M Eaton; M Elizabeth Fini Journal: Invest Ophthalmol Vis Sci Date: 2015-04 Impact factor: 4.799
Authors: Linda M Zangwill; Radha Ayyagari; Jeffrey M Liebmann; Christopher A Girkin; Robert Feldman; Harvey Dubiner; Keri A Dirkes; Matthew Holmann; Eunice Williams-Steppe; Naama Hammel; Luke J Saunders; Suzanne Vega; Kevin Sandow; Kathryn Roll; Rigby Slight; Daniel Auerbach; Brian C Samuels; Joseph F Panarelli; John P Mitchell; Lama A Al-Aswad; Sung Chul Park; Celso Tello; Jeremy Cotliar; Rajendra Bansal; Paul A Sidoti; George A Cioffi; Dana Blumberg; Robert Ritch; Nicholas P Bell; Lauren S Blieden; Garvin Davis; Felipe A Medeiros; Maggie C Y Ng; Swapan K Das; Nicholette D Palmer; Jasmin Divers; Carl D Langefeld; Barry I Freedman; Donald W Bowden; Mark A Christopher; Yii-der I Chen; Xiuqing Guo; Kent D Taylor; Jerome I Rotter; Robert N Weinreb Journal: Ophthalmology Date: 2018-02-01 Impact factor: 12.079
Authors: Xiaoyi Gao; Drew R Nannini; Kristen Corrao; Mina Torres; Yii-Der I Chen; Bao J Fan; Janey L Wiggs; Kent D Taylor; W James Gauderman; Jerome I Rotter; Rohit Varma Journal: Hum Mol Genet Date: 2016-11-15 Impact factor: 6.150
Authors: Alice E Davidson; Sek-Shir Cheong; Pirro G Hysi; Cristina Venturini; Vincent Plagnol; Jonathan B Ruddle; Hala Ali; Nicole Carnt; Jessica C Gardner; Hala Hassan; Else Gade; Lisa Kearns; Anne Marie Jelsig; Marie Restori; Tom R Webb; David Laws; Michael Cosgrove; Jens M Hertz; Isabelle Russell-Eggitt; Daniela T Pilz; Christopher J Hammond; Stephen J Tuft; Alison J Hardcastle Journal: PLoS One Date: 2014-08-05 Impact factor: 3.240