Genetic variation on chromosome 11 is associated with keratoconus

45 Importance Keratoconus is a condition in which the cornea progressively thins and protrudes in a conical 46 shape, severely affecting refraction and vision. It is a major indication for corneal transplantation. To 47 discover new genetic loci associated with keratoconus and to better understand the causative mechanism of 48 this disease, we performed a genome-wide association study (GWAS) on patients with keratoconus. 49 Objective To identify keratoconus genetic susceptibility regions in the human genome. 50 Design The discovery cohort was genotyped using the Illumina HumanCoreExome single nucleotide 51 polymorphism (SNP) array. Following quality control and data cleaning, genotypes were imputed against the 52 1000 Genomes Project reference panel (Phase III, version 5) and association analysis was completed using 53 PLINK. SNPs with P < 1 × 10 −6 were assessed for replication in three additional cohorts. We present findings from a GWAS of 522 patients with keratoconus, a relatively large sample for this complex disease. We show association and independent replication at the PNPLA2 region with keratoconus.

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