Using the Utah Population Database to assess familial risk of primary open angle glaucoma

PurposePrimary open angle glaucoma (POAG) is a leading cause of irreversible blindness in the elderly. Previous epidemiological studies have identified family history, ethnic origin, age, high intraocular pressure and diabetes mellitus as risk factors. However, it is difficult to assess the extent family history plays in this disease process. The Utah Population Database (UPDB), created by the University of Utah, has recently become a resource for which greater than 9 million records are available for use. The UPDB is divided into two major data sets from which family members can be identified, namely 1.6 million genealogy records and 2 million Utah birth certificates. This study utilizes these resources to assess the familial risk of POAG within the Utah Population.MethodsThe University of Utah's hospital and clinic records were searched for patients with primary and chronic open angle glaucoma (ICD9 codes 365.04 and 365.11) between the years 1995 and 2005. A case-control analysis was then performed with specialized UPDB software that was modified to constrain the control and pedigree populations to over 1 million University of Utah-UPDB linked records. Controls were matched to cases by gender and birth year (±2.5 years) with only one control being used per case. Population-attributable risk (PAR) to familial factors and relative risk (RR) were computed using conditional logistic regression (CLR).ResultsFrom the original 1.5 million medical records, 6198 patients with glaucoma were identified. Of these, 3391 met the inclusion criteria, which required patients to have at least one parent or one child in the UPDB. The PAR in this population was found to be 0.20, indicating 20% of the risk for glaucoma is attributable to genetic factors. CLR computations also showed a significantly increased relative risk (p < 0.05) in first cousins (RR = 1.45 (95% confidence interval (CI) 1.16-1.8)), second cousins (RR = 1.19 (95% CI 1.08-1.32)), siblings (RR = 3.76 (95% CI 2.66-5.31)), parents (RR = 6.25 (95% CI 3.94-9.9)) and children (RR = 6.77 (95% CI 3.39-13.5)).ConclusionsBased on these familial data, there is a significantly higher prevalence of glaucoma in both first and second generation relatives of those affected as compared to relatives in the control group. When compared with other epidemiologic studies, such as an analysis of first-degree relatives of patients from the Rotterdam study, which showed a PAR of 16%, our study actually demonstrates a greater familial contribution to glaucoma. The UPDB is a valuable and unique resource providing a large population from which to analyze the familial risk of glaucoma.

Research highlights► The Utah Population Database contains over 9 million family history records. ► The 1st and 2nd generations of glaucoma patients had much higher prevalence. ► We found that 20% of glaucoma is attributable to genetic factors.