Abstract

We conducted a meta-analysis of genome-wide association data to detect genes influencing age at menarche in 17,510 women. The strongest signal was at 9q31.2 (P = 1.7 × 10−9), where the nearest genes include TMEM38B, FKTN, FSD1L, TAL2 and ZNF462. The next best signal was near the LIN28B gene (rs7759938; P = 7.0 × 10−9), which also influences adult height. We provide the first evidence for common genetic variants influencing female sexual maturation.

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Acknowledgements

We are indebted to the participants and staff of the studies for their important contributions. Full individual study acknowledgements are listed in the Supplementary Methods.

Author information

Author notes

    • John R B Perry
    • , Lisette Stolk
    • , Nora Franceschini
    • , Kathryn L Lunetta
    • , Guangju Zhai
    • , Patrick F McArdle
    • , Albert V Smith
    • , Elizabeth A Streeten
    • , Tamara B Harris
    • , Anna Murray
    • , Tim D Spector
    • , Ellen W Demerath
    • , André G Uitterlinden
    •  & Joanne M Murabito

    These authors contributed equally to this work.

Affiliations

  1. Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK.

    • John R B Perry
    • , Michael N Weedon
    •  & Anna Murray
  2. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.

    • Lisette Stolk
    • , Karol Estrada
    • , Joyce van Meurs
    • , Fernando Rivadeneira
    • , Jenny A Visser
    •  & André G Uitterlinden
  3. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

    • Lisette Stolk
    • , Albert Hofman
    • , Fernando Rivadeneira
    •  & André G Uitterlinden
  4. Netherlands Genomics Initiative–sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Chapel Hill, North Carolina, USA.

    • Lisette Stolk
    • , Albert Hofman
    • , Joyce van Meurs
    • , Fernando Rivadeneira
    •  & André G Uitterlinden
  5. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.

    • Nora Franceschini
  6. The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Kathryn L Lunetta
    • , David Karasik
    • , Douglas P Kiel
    •  & Joanne M Murabito
  7. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Kathryn L Lunetta
    •  & Vivian Zhuang
  8. Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

    • Guangju Zhai
    • , Lynn Cherkas
    • , Nicole Soranzo
    • , Scott G Wilson
    •  & Tim D Spector
  9. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Patrick F McArdle
    • , Alan R Shuldiner
    •  & Elizabeth A Streeten
  10. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    • , Thor Aspelund
    • , Gudny Eiriksdottir
    •  & Vilmundur Gudnason
  11. University of Iceland, Reykjavik, Iceland.

    • Thor Aspelund
    •  & Vilmundur Gudnason
  12. Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy.

    • Stefania Bandinelli
  13. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Eric Boerwinkle
  14. Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Luigi Ferrucci
  15. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • Aaron R Folsom
    •  & Ellen W Demerath
  16. Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA.

    • Melissa Garcia
    • , Lenore J Launer
    •  & Tamara B Harris
  17. Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, USA.

    • David Karasik
    •  & Douglas P Kiel
  18. Laboratory of Neurogenetics, National Institute of Aging, Bethesda, Maryland, USA.

    • Michael A Nalls
    •  & Andrew Singleton
  19. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

    • Nicole Soranzo
  20. Medstar Research Institute, National Institute on Aging, Baltimore, Maryland, USA.

    • Toshiko Tanaka
  21. School of Medicine & Pharmacology, University of Western Australia and Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

    • Scott G Wilson
  22. Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Joanne M Murabito

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Contributions

Statistical analyses: J.R.B.P., L.S., N.F., K.L.L., G.Z., P.F.M., A.V.S., T.A., K.E., V.G., F.R., N.S., T.T., M.N.W. and V.Z. Sample collection, preparation: N.F., A.V.S., T.A., S.B., E.B., L.C., G.E., L.F., A.R.F., V.G., A.H., S.G.W., T.B.H., T.D.S., E.W.D. and A.G.U. Genotyping: E.B., F.R., A.S., N.S. and A.G.U. Manuscript writing: J.R.B.P., L.S., P.F.M., A.V.S., T.A., G.E., V.G., E.A.S., A.M., E.W.D. and A.G.U. Review and revision of the manuscript: J.R.B.P., L.S., N.F., K.L.L., G.Z., P.F.M., A.V.S., T.A., S.B., E.B., L.C., G.E., K.E., L.F., A.R.F., M.G., V.G., A.H., D.K., D.P.K., L.J.L., J.v.M., M.A.N., F.R., A.R.S., A.S., N.S., T.T., J.A.V., M.N.W., S.G.W., V.Z., E.A.S., T.B.H., A.M., T.D.S., E.W.D., A.G.U. and J.M.M. Intellectual input: J.R.B.P., L.S., N.F., K.L.L., P.F.M., E.B., G.E., A.R.F., V.G., D.K., D.P.K., J.A.V., S.G.W., A.M., A.G.U. and J.M.M. Study design: J.R.B.P., L.S., K.L.L., G.Z., A.V.S., T.A., S.B., G.E., L.F., V.G., A.H., D.K., D.P.K., A.M., T.D.S., A.G.U. and J.M.M.

Corresponding author

Correspondence to André G Uitterlinden.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1 and 2, Supplementary Tables 1–4, Supplementary Methods and Supplementary Note

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DOI

https://doi.org/10.1038/ng.386

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