title: 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: 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.
  
  
  
  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.
  
  
  
  The genetic risk score was associated with self-reported ANM (P = 2.2 × 10) 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 10 percentile or highest 90 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).
  
  
  
  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.
authors.affiliation: 1Department of Ophthalmology, Massachusetts Eye and Ear Infirmary 2Channing Division of Network Medicine, Brigham and Women's Hospital 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard Medical School, Boston, MA 4Department of Epidemiology and Biostatistics 5Institute of Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH 6Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 7Department of Ophthalmology 8Department of Medicine, Duke University, Duke University Medical Center, Durham, NC 9Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 10Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 11Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI 12Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA 13Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IO 14Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 15Department of Ophthalmology, WVU Eye Institute, Morgantown, WV 16Scripps Genome Center, University of California at San Diego, San Diego, CA 17Emmes Corporation, Chevy Chase, MD 18Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 19Department of Ophthalmology, Stanford University, Palo Alto, CA 20Department of Ophthalmology, Mayo Clinic, Rochester, MN 21Wills Eye Institute, Philadelphia, PA 22Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY 23Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH 24Department of Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, NE 25Department of Genetics; Stanford University, Palo Alto, CA 26Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD 27Department of Ophthalmology, Hamilton Eye Center; University of California at San Diego, San Diego, CA 28Department of Cellular Biology & Anatomy, Augusta University, Augusta, GA.
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mesh_terms: D000367:Age Factors; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014481:United States