Familial risk and interaction with hypertension and hyperglycemia in primary open-angle glaucoma

Although there is a genetic component to primary open-angle glaucoma (POAG) susceptibility, few studies have investigated interactions between genetic and environmental factors. We aimed to quantify the familial risk of POAG and estimate disease risk among individuals with a positive family history and either hypertension or hyperglycemia, as well as assess their interactions. Using the National Health Insurance database, which includes information on familial relationships and lifestyle risk factors, we identified 6,217,057 individuals with first-degree relatives (FDRs) from 2002-2018. We calculated familial risk using hazard ratios (HRs) with 95% confidence intervals (CIs) which compare the risk of individuals with and without affected FDRs. Disease risk was estimated among individuals with both a positive family history and hypertension or hyperglycemia, and interactions were assessed on an additive scale. Individuals with an affected parent had a 3.13-fold (95% CI 2.74 –3.58) increased risk of disease compared to those with unaffected parents. Individuals with affected father, mother, or both affected parents showed HRs (95% CI) of 3.50 (2.86 –4.30), 2.87 (2.41 –3.44) and 4.88 (1.83 –12.98), respectively. Familial risk adjusted for lifestyle factors decreased slightly (HR 3.14), suggesting that genetic component is the predominant driver in the familial aggregation. Individuals with a positive family history and either hypertension or hyperglycemia had a markedly elevated risk of disease, with HRs of 3.42 (95% CI 2.49 –4.69) and 3.27 (95% CI 2.15 –4.97), respectively. Hypertensive or hyperglycemic individuals with a positive family history may be considered a high-risk group and glaucoma screening may be considered.