Journal article

Recurrent Rare Copy Number Variants Increase Risk for Esotropia

Mary C Whitman, Silvio Alessandro Di Gioia, Wai-Man Chan, Alon Gelber, Brandon M Pratt, Jessica L Bell, Thomas E Collins, James A Knowles, Christopher Armoskus, Michele Pato, Carlos Pato, Sherin Shaaban, Sandra Staffieri, Sarah MacKinnon, Gail DE Maconachie, James E Elder, Elias I Traboulsi, Irene Gottlob, David A Mackey, David G Hunter Show all



Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and break..

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Awarded by National Eye Institute

Awarded by National Institute of Child Health and Development

Awarded by National Heart, Lung and Blood Institute grant

Awarded by National Human Genome Research Institute

Funding Acknowledgements

Supported by the National Eye Institute [5K08EY027850, R01EY15298], National Institute of Child Health and Development [U54HD090255], and the Children's Hospital Ophthalmology Foundation [Faculty Discovery Award]. Sequencing was provided by the Broad Institute of MIT and Harvard Center for Medelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141. A portion of the dataset(s) used for the analyses described in this manuscript were obtained from the Genetics of Fuchs' Endothelial Corneal Dystrophy (FECD) Study found at through dbGaP accession number phs000421.v1.p1. The grants that have funded the enrollment of the cases and controls to be used in this GWAS are: R01EY016514 (DUEC, PI: Gordon Klintworth), R01EY016482 (CWRU, PI: Sudha Iyengar), and 1X01HG006619-01 (PI: Sudha Iyengar, Natalie Afshari). ECE is a Howard Hughes Medical Institute Investigator. The sponsors or funding organizations had no role in the design or conduct of this research.