1. Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample
- Author
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Pasquale, Louis, Aschard, Hugues, Kang, Jae, Bailey, Jessica, Lindström, Sara, Chasman, Daniel, Christen, William, Allingham, R Rand, Ashley-Koch, Allison, Lee, Richard, Moroi, Sayoko, Brilliant, Murray, Wollstein, Gadi, Schuman, Joel, Fingert, John, Budenz, Donald, Realini, Tony, Gaasterland, Terry, Gaasterland, Douglas, Scott, William, Singh, Kuldev, Sit, Arthur, Igo, Robert, Song, Yeunjoo, Hark, Lisa, Ritch, Robert, Rhee, Douglas, Gulati, Vikas, Havens, Shane, Vollrath, Douglas, Zack, Donald, Medeiros, Felipe, Weinreb, Robert, Pericak-Vance, Margaret, Liu, Yutao, Kraft, Peter, Richards, Julia, Rosner, Bernard, Hauser, Michael, Haines, Jonathan, Wiggs, Janey, Allingham, R. Rand, Harvard Medical School [Boston] (HMS), Brigham & Women’s Hospital [Boston] (BWH), Harvard T.H. Chan School of Public Health, Case Western Reserve University [Cleveland], Program in Genetic Epidemiology and Statistical Genetics (PGESG - BOSTON), Harvard School of Public Health, Brigham and Women's Hospital [Boston], Lawrence Livermore National Laboratory (LLNL), The NIH/NEI R01EY022305 (J.L.W.) supports data collection and analysis for the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD) consortium. Support for collection of cases, controls, and analysis for individual datasets is as follows. Genotyping services for the predecessor National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study were provided by the Center for Inherited Disease Research (CIDR) and were supported by the National Eye Institute (NEI) through grant HG005259-01 (J.L.W.). In addition, CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University—contract number HHSN268200782096C. Genotyping for the Mass Eye and Ear dataset and some Nurses Health Study (NHS) and Health Professionals Follow-up Study (HPFS) participants that formed the Glaucoma Genes and Environment (GLAUGEN) study was completed at the Broad Institute and supported by GENEVA project grant HG004728 (L.R.P.) and U01-HG004424 (Broad Institute). NIH/NHGRI U01 HG004446 (C Laurie) supported genotype data cleaning and analysis for the GLAUGEN study. The NEI through ARRA grants 3R01EY015872-05S1 (J.L.W.) and 3R01EY019126-02S1 (M.A.H.) supported the collection and processing samples for the NEIGHBOR dataset. The funding for the collection of NEIGHBOR cases and controls was provided by NIH grants: EY015543 (R.R.A.), U02HG004608 (M.H.B.), HG006389 (M.H.B.), UL1TR000427 (M.H.B.), EY006827 (D.G.), HL73042, HL073389, EY13315 (M.A.H.), CA87969, CA49449, CA55075, EY009149 (PR Lichter), HG004608 (C McCarty), EY008208 (F.M.), EY015473 (L.R.P.), EY012118 (M.A.P.-V.), EY015682 (T.R.), EY011671 (J.E.R.), EY09580 (J.E.R.), EY013178 (J.S.S.), EY010886 (J.L.W.), EY009847 (J.L.W.), EY011008, EY144428 (K Zhang), EY144448 (K Zhang), EY18660 (K Zhang), and Research to Prevent Blindness (multiple institutions). The collection of Marshfield clinic cases and controls was supported by 1U02HG004608-01, 5U01HG006389-02, and NCATS/NIH grant UL1TR000427. In addition, some NHS/HPFS cases and controls and analysis of genome-wide data were supported by R01 CA131332 (RM Tamimi, I De Vivo), UM1 CA186107, UM1 CA167552, R01 CA49449, P01 CA87969. The Women's Genome Health Study (WGHS) is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Foundation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. POAG case identification in Women's Genome Health Study was supported by 3RO1 EY015473-05S1 (LR Pasquale). Blood collection at New York Eye & Ear Infirmary was supported by the New York Glaucoma Research Institute., H.A., J.N.C.B., S.L., D.L.C., W.G.C., A.A.-K., S.E.M., D.G., M.H.B., G.W., R.P.I., Y.E.S., L.H., S.H., D.V., M.A.P.-V., and J.E.R. have no conflicts to declare. J.L.W., J.H.K., R.R.A., M.A.H., R.K.L., T.G., V.G., D.J.Z., Y.L., P.K., and B.A.R. sole disclosure is that they receive grant support from NIH. L.R.P. received grant support from NIH and has been a speaker for Allergan. He also served as a paid consultant to Novartis and to Bausch + Lomb. He has received support to travel to meetings by The Glaucoma Foundation (NYC), Glaukos and Aerie Pharmaceuticals. J.S.S. received grant support from NIH and is an inventor on a patent. J.F. received grant support from NIH and Regeneron. D.L.B. received consulting fees from Alcon Labs and travel support from New World Medical, Inc. He is also compensated for Data Safety Monitoring Board activity from Ivantis. He received grant support from New World Medical. T.R. received grant support from NIH and is a consultant for Alcon, Alimera, Bausch and Lomb, Reichert, Sensimed, and Inotek. W.K.S. holds a patent regarding the use of genetic data for risk assessment in age-related macula degeneration (Duke University). He received grant support from NIH, Florida Biomedical Research Program and the American Health Assistance Foundation. K.S. is a consultant to Alcon, Allergan, Santen, and Shire. A.H.S. serves as a consultant to Allergan, Alcon and Sensimed. He has received research support from NIH, Aerie Pharmaceuticals, and Glaukos. R.R. is on the advisory board of Isonic Inc, Intelon Optics and Xoma (US) LLC. He serves as consultant for Aeon Astron Europe B.V., Diopsyc, Inc, GLIA LLC, Gerson Lehrman Group, Guardian Health Sciences and Mobius Therapeutics. He is on the Board of Directors for International Eye Wellness Institute and receives royalties from Ocular Instruments. D.J.R. received research support from Merck, Allergan, Ivantis, and Glaukos. He is on the Scientific Advisory Board of Aerie and Transcend and is on the Data Safety Monitoring Board of Sanofi. F.M. received research support from Carl-Zeiss Meditec, Heidelberg Engineering, Allergan, Topcon, Reichert and Genentech. R.N.W. had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Alcon, Allergan, Bausch & Lomb Incorporated, ForSight VISION5, and Valeant, Contracted Research: Genentech, Inc, and and Quark. J.L.H. receives travel support and speaker honoraria from Novartis. He has received royalties from John Wiley and Sons and Athena Diagnostics. The NIH supports his research
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0301 basic medicine ,Percentile ,Aging ,genetic structures ,MESH: Menopause ,Neurodegenerative ,MESH: Risk Assessment ,Medical and Health Sciences ,MESH: Genotype ,0302 clinical medicine ,Risk Factors ,MESH: Risk Factors ,Reproductive history ,MESH: Genetic Variation ,Genetic risk ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,Natural menopause ,MESH: Middle Aged ,Age Factors ,Obstetrics and Gynecology ,Middle Aged ,Genetic risk score ,3. Good health ,Open-Angle ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Female ,Menopause ,Primary open-angle glaucoma ,[STAT.ME]Statistics [stat]/Methodology [stat.ME] ,Glaucoma, Open-Angle ,medicine.medical_specialty ,Genotype ,Age at natural menopause ,Risk Assessment ,03 medical and health sciences ,medicine ,Genetics ,MESH: United States ,Humans ,Obstetrics & Reproductive Medicine ,Eye Disease and Disorders of Vision ,Gynecology ,MESH: Age Factors ,MESH: Humans ,business.industry ,Human Genome ,Genetic variants ,Neurosciences ,Genetic Variation ,Glaucoma ,Odds ratio ,Original Articles ,Confidence interval ,United States ,eye diseases ,030104 developmental biology ,Good Health and Well Being ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,030221 ophthalmology & optometry ,MESH: Glaucoma, Open-Angle ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,business ,MESH: Female ,Demography - Abstract
Supplemental Digital Content is available in the text, 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.
- Published
- 2017