A genome-wide association study of early menopause and the combined impact of identified variants

John R B Perry, Tanguy Corre, Tõnu Esko, Daniel I. Chasman, Krista Fischer, Nora Franceschini, Chunyan He, Zoltan Kutalik, Massimo Mangino, Lynda M. Rose, Albert Vernon smith, Lisette Stolk, Patrick Sulem, Michael N. Weedon, Wei V. Zhuang, Alice Arnold, Alan Ashworth, Sven Bergmann, Julie E. Buring, Andrea Burri & 46 others Constance Chen, Marilyn C. Cornelis, David J. Couper, Mark O. Goodarzi, Vilmundur Gudnason, Tamara Harris, Albert Hofman, Michael Jones, Peter Kraft, Lenore Launer, Joop S E Laven, Guo Li, Barbara Mcknight, Corrado Masciullo, Lili Milani, Nicholas Orr, Bruce M. Psaty, Paul M. Ridker, Fernando Rivadeneira, Cinzia Sala, Andres Salumets, Minouk Schoemaker, Michela Traglia, Gérard Waeber, Stephen J. Chanock, Ellen W. Demerath, Melissa Garcia, Susan E. Hankinson, Frank B. Hu, David J. Hunter, Kathryn L. Lunetta, Andres Metspalu, Grant W. Montgomery, Joanne M. Murabito, Anne B. Newman, Ken K. Ong, Tim D. Spector, Kari Stefansson, Anthony J. Swerdlow, Unnur Thorsteinsdottir, Rob M. Van dam, André G. Uitterlinden, Jenny A. Visser, Peter Vollenweider, Daniela Toniolo, Anna Murray

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ~30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.

Original languageEnglish
Article numberdds551
Pages (from-to)1465-1472
Number of pages8
JournalHuman Molecular Genetics
Volume22
Issue number7
DOIs
Publication statusPublished - Apr 2013

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Genome-Wide Association Study
Menopause
Primary Ovarian Insufficiency
Western World
Infertility
Single Nucleotide Polymorphism
Meta-Analysis
Smoking
Pregnancy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Perry, J. R. B., Corre, T., Esko, T., Chasman, D. I., Fischer, K., Franceschini, N., ... Murray, A. (2013). A genome-wide association study of early menopause and the combined impact of identified variants. Human Molecular Genetics, 22(7), 1465-1472. [dds551]. https://doi.org/10.1093/hmg/dds551

A genome-wide association study of early menopause and the combined impact of identified variants. / Perry, John R B; Corre, Tanguy; Esko, Tõnu; Chasman, Daniel I.; Fischer, Krista; Franceschini, Nora; He, Chunyan; Kutalik, Zoltan; Mangino, Massimo; Rose, Lynda M.; Vernon smith, Albert; Stolk, Lisette; Sulem, Patrick; Weedon, Michael N.; Zhuang, Wei V.; Arnold, Alice; Ashworth, Alan; Bergmann, Sven; Buring, Julie E.; Burri, Andrea; Chen, Constance; Cornelis, Marilyn C.; Couper, David J.; Goodarzi, Mark O.; Gudnason, Vilmundur; Harris, Tamara; Hofman, Albert; Jones, Michael; Kraft, Peter; Launer, Lenore; Laven, Joop S E; Li, Guo; Mcknight, Barbara; Masciullo, Corrado; Milani, Lili; Orr, Nicholas; Psaty, Bruce M.; Ridker, Paul M.; Rivadeneira, Fernando; Sala, Cinzia; Salumets, Andres; Schoemaker, Minouk; Traglia, Michela; Waeber, Gérard; Chanock, Stephen J.; Demerath, Ellen W.; Garcia, Melissa; Hankinson, Susan E.; Hu, Frank B.; Hunter, David J.; Lunetta, Kathryn L.; Metspalu, Andres; Montgomery, Grant W.; Murabito, Joanne M.; Newman, Anne B.; Ong, Ken K.; Spector, Tim D.; Stefansson, Kari; Swerdlow, Anthony J.; Thorsteinsdottir, Unnur; Van dam, Rob M.; Uitterlinden, André G.; Visser, Jenny A.; Vollenweider, Peter; Toniolo, Daniela; Murray, Anna.

In: Human Molecular Genetics, Vol. 22, No. 7, dds551, 04.2013, p. 1465-1472.

Research output: Contribution to journalArticle

Perry, JRB, Corre, T, Esko, T, Chasman, DI, Fischer, K, Franceschini, N, He, C, Kutalik, Z, Mangino, M, Rose, LM, Vernon smith, A, Stolk, L, Sulem, P, Weedon, MN, Zhuang, WV, Arnold, A, Ashworth, A, Bergmann, S, Buring, JE, Burri, A, Chen, C, Cornelis, MC, Couper, DJ, Goodarzi, MO, Gudnason, V, Harris, T, Hofman, A, Jones, M, Kraft, P, Launer, L, Laven, JSE, Li, G, Mcknight, B, Masciullo, C, Milani, L, Orr, N, Psaty, BM, Ridker, PM, Rivadeneira, F, Sala, C, Salumets, A, Schoemaker, M, Traglia, M, Waeber, G, Chanock, SJ, Demerath, EW, Garcia, M, Hankinson, SE, Hu, FB, Hunter, DJ, Lunetta, KL, Metspalu, A, Montgomery, GW, Murabito, JM, Newman, AB, Ong, KK, Spector, TD, Stefansson, K, Swerdlow, AJ, Thorsteinsdottir, U, Van dam, RM, Uitterlinden, AG, Visser, JA, Vollenweider, P, Toniolo, D & Murray, A 2013, 'A genome-wide association study of early menopause and the combined impact of identified variants', Human Molecular Genetics, vol. 22, no. 7, dds551, pp. 1465-1472. https://doi.org/10.1093/hmg/dds551
Perry JRB, Corre T, Esko T, Chasman DI, Fischer K, Franceschini N et al. A genome-wide association study of early menopause and the combined impact of identified variants. Human Molecular Genetics. 2013 Apr;22(7):1465-1472. dds551. https://doi.org/10.1093/hmg/dds551
Perry, John R B ; Corre, Tanguy ; Esko, Tõnu ; Chasman, Daniel I. ; Fischer, Krista ; Franceschini, Nora ; He, Chunyan ; Kutalik, Zoltan ; Mangino, Massimo ; Rose, Lynda M. ; Vernon smith, Albert ; Stolk, Lisette ; Sulem, Patrick ; Weedon, Michael N. ; Zhuang, Wei V. ; Arnold, Alice ; Ashworth, Alan ; Bergmann, Sven ; Buring, Julie E. ; Burri, Andrea ; Chen, Constance ; Cornelis, Marilyn C. ; Couper, David J. ; Goodarzi, Mark O. ; Gudnason, Vilmundur ; Harris, Tamara ; Hofman, Albert ; Jones, Michael ; Kraft, Peter ; Launer, Lenore ; Laven, Joop S E ; Li, Guo ; Mcknight, Barbara ; Masciullo, Corrado ; Milani, Lili ; Orr, Nicholas ; Psaty, Bruce M. ; Ridker, Paul M. ; Rivadeneira, Fernando ; Sala, Cinzia ; Salumets, Andres ; Schoemaker, Minouk ; Traglia, Michela ; Waeber, Gérard ; Chanock, Stephen J. ; Demerath, Ellen W. ; Garcia, Melissa ; Hankinson, Susan E. ; Hu, Frank B. ; Hunter, David J. ; Lunetta, Kathryn L. ; Metspalu, Andres ; Montgomery, Grant W. ; Murabito, Joanne M. ; Newman, Anne B. ; Ong, Ken K. ; Spector, Tim D. ; Stefansson, Kari ; Swerdlow, Anthony J. ; Thorsteinsdottir, Unnur ; Van dam, Rob M. ; Uitterlinden, André G. ; Visser, Jenny A. ; Vollenweider, Peter ; Toniolo, Daniela ; Murray, Anna. / A genome-wide association study of early menopause and the combined impact of identified variants. In: Human Molecular Genetics. 2013 ; Vol. 22, No. 7. pp. 1465-1472.
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