A Genome-Wide Association Study of Intraocular Pressure in Latinos

Intraocular pressure (IOP) is a major, as well as the only modifiable, risk factor for glaucoma. With an expected increase in the number of individuals affected by glaucoma, understanding genetic factors related to IOP may aid in developing screening and prevention strategies for this disease. The purpose of this thesis is to identify genetic variants associated with IOP in Latinos. A genome-wide association study (GWAS) was conducted using data collected from 3,374 Latinos recruited by the Los Angeles Latino Eye Study (LALES). Linear regression analysis was performed adjusting for age, gender, and principal components of genetic ancestry. Results from the analysis yielded five suggestive single nucleotide polymorphisms (SNPs) that were associated with IOP. The top SNP associated with IOP was located at 21q21.2 (P=8.80×10-8) on chromosome 21 between TUBAP and VN2R20P and was associated with a 1.33 mmHg increase in IOP per effect allele. The second most significant SNP, rs12591689 (P=5.23×10-6), was located on chromosome 15 in PCSK6 and was associated with a 0.31 mmHg increase in IOP per effect allele. This study represents the first GWAS of IOP in Latinos, and both replicated previously reported and identified new genetic variants associated with IOP. Further replication studies are needed, and implications for these genetic variants include screening and identifying individuals who harbor these polymorphisms that increase IOP.