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

Louis R. Pasquale, Hugues Aschard, Jae H. Kang, Jessica N.Cooke Bailey, Sara Lindström, Daniel I. Chasman, William G. Christen, R. Rand Allingham, Allison Ashley-Koch, Richard K. Lee, Sayoko E. Moroi, Murray H. Brilliant, Gadi Wollstein, Joel S. Schuman, John Fingert, Donald L. Budenz, Tony Realini, Terry Gaasterland, Douglas Gaasterland, William K. ScottKuldev Singh, Arthur J. Sit, Robert P. Igo, Yeunjoo E. Song, Lisa Hark, Robert Ritch, Douglas J. Rhee, Vikas Gulati, Shane Havens, Douglas Vollrath, Donald J. Zack, Felipe Medeiros, Robert N. Weinreb, Margaret A. Pericak-Vance, Yutao Liu, Peter Kraft, Julia E. Richards, Bernard A. Rosner, Michael A. Hauser, Jonathan L. Haines, Janey L. Wiggs

Research output: Contribution to journalArticle

2 Citations (Scopus)

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). 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.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalMenopause
Volume24
Issue number2
DOIs
StatePublished - Jan 1 2017

Fingerprint

Menopause
Odds Ratio
Confidence Intervals
National Eye Institute (U.S.)
Primary Open Angle Glaucoma
Reproductive History
Medical Genetics
Glaucoma
Nurses
Genotype
Databases
Phenotype
Health

Keywords

  • Age at natural menopause
  • Genetic risk score
  • Primary open-angle glaucoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Pasquale, L. R., Aschard, H., Kang, J. H., Bailey, J. N. C., Lindström, S., Chasman, D. I., ... Wiggs, J. L. (2017). Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample. Menopause, 24(2), 150-156. https://doi.org/10.1097/GME.0000000000000741

Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample. / Pasquale, Louis R.; Aschard, Hugues; Kang, Jae H.; Bailey, Jessica N.Cooke; Lindström, Sara; Chasman, Daniel I.; Christen, William G.; Allingham, R. Rand; Ashley-Koch, Allison; Lee, Richard K.; Moroi, Sayoko E.; Brilliant, Murray H.; Wollstein, Gadi; Schuman, Joel S.; Fingert, John; Budenz, Donald L.; Realini, Tony; Gaasterland, Terry; Gaasterland, Douglas; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Igo, Robert P.; Song, Yeunjoo E.; Hark, Lisa; Ritch, Robert; Rhee, Douglas J.; Gulati, Vikas; Havens, Shane; Vollrath, Douglas; Zack, Donald J.; Medeiros, Felipe; Weinreb, Robert N.; Pericak-Vance, Margaret A.; Liu, Yutao; Kraft, Peter; Richards, Julia E.; Rosner, Bernard A.; Hauser, Michael A.; Haines, Jonathan L.; Wiggs, Janey L.

In: Menopause, Vol. 24, No. 2, 01.01.2017, p. 150-156.

Research output: Contribution to journalArticle

Pasquale, LR, Aschard, H, Kang, JH, Bailey, JNC, Lindström, S, Chasman, DI, Christen, WG, Allingham, RR, Ashley-Koch, A, Lee, RK, Moroi, SE, Brilliant, MH, Wollstein, G, Schuman, JS, Fingert, J, Budenz, DL, Realini, T, Gaasterland, T, Gaasterland, D, Scott, WK, Singh, K, Sit, AJ, Igo, RP, Song, YE, Hark, L, Ritch, R, Rhee, DJ, Gulati, V, Havens, S, Vollrath, D, Zack, DJ, Medeiros, F, Weinreb, RN, Pericak-Vance, MA, Liu, Y, Kraft, P, Richards, JE, Rosner, BA, Hauser, MA, Haines, JL & Wiggs, JL 2017, 'Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample', Menopause, vol. 24, no. 2, pp. 150-156. https://doi.org/10.1097/GME.0000000000000741
Pasquale, Louis R. ; Aschard, Hugues ; Kang, Jae H. ; Bailey, Jessica N.Cooke ; Lindström, Sara ; Chasman, Daniel I. ; Christen, William G. ; Allingham, R. Rand ; Ashley-Koch, Allison ; Lee, Richard K. ; Moroi, Sayoko E. ; Brilliant, Murray H. ; Wollstein, Gadi ; Schuman, Joel S. ; Fingert, John ; Budenz, Donald L. ; Realini, Tony ; Gaasterland, Terry ; Gaasterland, Douglas ; Scott, William K. ; Singh, Kuldev ; Sit, Arthur J. ; Igo, Robert P. ; Song, Yeunjoo E. ; Hark, Lisa ; Ritch, Robert ; Rhee, Douglas J. ; Gulati, Vikas ; Havens, Shane ; Vollrath, Douglas ; Zack, Donald J. ; Medeiros, Felipe ; Weinreb, Robert N. ; Pericak-Vance, Margaret A. ; Liu, Yutao ; Kraft, Peter ; Richards, Julia E. ; Rosner, Bernard A. ; Hauser, Michael A. ; Haines, Jonathan L. ; Wiggs, Janey L. / Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample. In: Menopause. 2017 ; Vol. 24, No. 2. pp. 150-156.
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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). 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.",
keywords = "Age at natural menopause, Genetic risk score, Primary open-angle glaucoma",
author = "Pasquale, {Louis R.} and Hugues Aschard and Kang, {Jae H.} and Bailey, {Jessica N.Cooke} and Sara Lindstr{\"o}m and Chasman, {Daniel I.} and Christen, {William G.} and Allingham, {R. Rand} and Allison Ashley-Koch and Lee, {Richard K.} and Moroi, {Sayoko E.} and Brilliant, {Murray H.} and Gadi Wollstein and Schuman, {Joel S.} and John Fingert and Budenz, {Donald L.} and Tony Realini and Terry Gaasterland and Douglas Gaasterland and Scott, {William K.} and Kuldev Singh and Sit, {Arthur J.} and Igo, {Robert P.} and Song, {Yeunjoo E.} and Lisa Hark and Robert Ritch and Rhee, {Douglas J.} and Vikas Gulati and Shane Havens and Douglas Vollrath and Zack, {Donald J.} and Felipe Medeiros and Weinreb, {Robert N.} and Pericak-Vance, {Margaret A.} and Yutao Liu and Peter Kraft and Richards, {Julia E.} and Rosner, {Bernard A.} and Hauser, {Michael A.} and Haines, {Jonathan L.} and Wiggs, {Janey L.}",
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TY - JOUR

T1 - Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample

AU - Pasquale, Louis R.

AU - Aschard, Hugues

AU - Kang, Jae H.

AU - Bailey, Jessica N.Cooke

AU - Lindström, Sara

AU - Chasman, Daniel I.

AU - Christen, William G.

AU - Allingham, R. Rand

AU - Ashley-Koch, Allison

AU - Lee, Richard K.

AU - Moroi, Sayoko E.

AU - Brilliant, Murray H.

AU - Wollstein, Gadi

AU - Schuman, Joel S.

AU - Fingert, John

AU - Budenz, Donald L.

AU - Realini, Tony

AU - Gaasterland, Terry

AU - Gaasterland, Douglas

AU - Scott, William K.

AU - Singh, Kuldev

AU - Sit, Arthur J.

AU - Igo, Robert P.

AU - Song, Yeunjoo E.

AU - Hark, Lisa

AU - Ritch, Robert

AU - Rhee, Douglas J.

AU - Gulati, Vikas

AU - Havens, Shane

AU - Vollrath, Douglas

AU - Zack, Donald J.

AU - Medeiros, Felipe

AU - Weinreb, Robert N.

AU - Pericak-Vance, Margaret A.

AU - Liu, Yutao

AU - Kraft, Peter

AU - Richards, Julia E.

AU - Rosner, Bernard A.

AU - Hauser, Michael A.

AU - Haines, Jonathan L.

AU - Wiggs, Janey L.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Age at natural menopause

KW - Genetic risk score

KW - Primary open-angle glaucoma

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