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Meta-analysis of genome-wide association data identifies two loci influencing age at menarche

Nature Genetics volume 41, pages 648–650 (2009)Cite this article

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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Figure 1: Genomic context (based on NCBI B36) of the top two independent signals at 9q31.2 and 6q21 plotted against association −log10 P values.

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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

  1. 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 and Joanne M Murabito: These authors contributed equally to this work.

Authors and 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. University of Western Australia and Department of Endocrinology & Diabetes, School of Medicine & Pharmacology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

    Scott G Wilson

  22. Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts, USA

    Joanne M Murabito

Authors
  1. John R B Perry
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  2. Lisette Stolk
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  4. Kathryn L Lunetta
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  5. Guangju Zhai
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  6. Patrick F McArdle
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  7. Albert V Smith
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  9. Stefania Bandinelli
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  10. Eric Boerwinkle
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  15. Aaron R Folsom
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  16. Melissa Garcia
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  17. Vilmundur Gudnason
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  18. Albert Hofman
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  19. David Karasik
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  20. Douglas P Kiel
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  21. Lenore J Launer
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  22. Joyce van Meurs
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  23. Michael A Nalls
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  24. Fernando Rivadeneira
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  25. Alan R Shuldiner
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  26. Andrew Singleton
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  27. Nicole Soranzo
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  28. Toshiko Tanaka
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  29. Jenny A Visser
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  30. Michael N Weedon
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  31. Scott G Wilson
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  32. Vivian Zhuang
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  33. Elizabeth A Streeten
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  34. Tamara B Harris
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  35. Anna Murray
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  36. Tim D Spector
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  37. Ellen W Demerath
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  38. André G Uitterlinden
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  39. 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

Supplementary Text and Figures

Supplementary Figures 1 and 2, Supplementary Tables 1–4, Supplementary Methods and Supplementary Note (PDF 437 kb)

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Perry, J., Stolk, L., Franceschini, N. et al. Meta-analysis of genome-wide association data identifies two loci influencing age at menarche. Nat Genet 41, 648–650 (2009). https://doi.org/10.1038/ng.386

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