Journal
MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
Volume 24, Issue 2, Pages 150-156Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/GME.0000000000000741
Keywords
Age at natural menopause; Genetic risk score; Primary open-angle glaucoma
Categories
Funding
- National Eye Institute (NEI) [HG005259-01]
- National Institutes of Health [HHSN268200782096C]
- NEI through ARRA grants [3R01EY015872-05S1, 3R01EY019126-02S1]
- NIH grants [EY015543, U02HG004608, HG006389, UL1TR000427, EY006827, HL073389, HL73042, EY13315, CA87969, CA49449, CA55075, EY009149, HG004608, EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178, EY010886, EY009847, EY011008, EY144428, EY144448, EY18660]
- Research to Prevent Blindness (multiple institutions)
- NCATS/NIH grant [UL1TR000427]
- National Heart, Lung, and Blood Institute [HL043851, HL080467]
- National Cancer Institute [CA047988]
- Donald W. Reynolds Foundation
- Foundation Leducq
- Amgen
- New York Glaucoma Research Institute
- GENEVA project grant [HG004728, U01-HG004424]
- [1U02HG004608-01]
- [5U01HG006389-02]
- [R01 CA131332]
- [UM1 CA186107]
- [UM1 CA167552]
- [R01 CA49449]
- [P01 CA87969]
- [3RO1 EY015473-05S1]
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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). Conclusions: 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.
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