Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample

Abstract

Objective Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. Methods Using data from the Nurses’ Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. Results The genetic risk score was associated with self-reported ANM (p=2.2×10−77) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR)=1.002; 95% Confidence Interval (CI): 0.998, 1.007; p=0.28). No single genetic variant in the panel achieved nominal association with POAG (p≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10th percentile or highest 90th percentile of genetic risk score with POAG (OR=0.75; 95% CI: 0.47, 1.21; p=0.23 and OR=1.10; 95% CI: 0.72, 1.69; p=0.65, respectively). Conclusion A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.

Retina-Targeted Delivery of 17β-Estradiol by the Topically Applied DHED Prodrug

“…The beneficial effects of endogenous or exogenously applied 17β-estradiol (E2) for eye health have been shown by basic science studies [1][2][3][4][5] and epidemiological observations [6][7][8]. Our interest in this regard stems from an unmet medical need for ocular neuroprotection [3,9].…”

The Association of Female Reproductive Factors with Glaucoma and Related Traits

“… 47 The number of studies reporting each of these subtypes individually did not make a subanalysis realistic in this review, although an effort was made to do so. A recent genetic risk score of 18 single nucleotide polymorphisms strongly associated with the age at natural menopause (explaining 4.8% of the variation in age at natural menopause) was not found to be associated with POAG, 48 suggesting no likely underlying genetic association for the findings from the included observational studies. Interestingly, 1 included study found that individuals who underwent surgically induced menopause (via bilateral oophorectomy) before the age of 43 had 1.6 times the risk of glaucoma (broadly defined) compared with a referent group of age-matched women who did not undergo oophorectomy (OR, 1.6; 95% CI, 1.15–2.23).…”