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Many sequence variants affecting diversity of adult human height

Nature Genetics 40, 609–615 (2008) | Download Citation

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Abstract

Adult human height is one of the classical complex human traits1. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians2 and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses3,4,5, and the strongest association was with SNPs in the ZBTB38 gene.

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Author information

Affiliations

  1. deCODE Genetics, 101 Reykjavik, Iceland.

    • Daniel F Gudbjartsson
    • , G Bragi Walters
    • , Gudmar Thorleifsson
    • , Hreinn Stefansson
    • , Bjarni V Halldorsson
    • , Pasha Zusmanovich
    • , Patrick Sulem
    • , Steinunn Thorlacius
    • , Arnaldur Gylfason
    • , Stacy Steinberg
    • , Anna Helgadottir
    • , Andres Ingason
    • , Valgerdur Steinthorsdottir
    • , Thorunn Rafnar
    • , Jeffrey Gulcher
    • , Augustine Kong
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson

  2. Reykjavik University, 103 Reykjavik, Iceland.

    • Bjarni V Halldorsson

  3. Icelandic Cancer Registry, 105 Reykjavik, Iceland.

    • Elinborg J Olafsdottir
    • , Gudridur H Olafsdottir
    •  & Laufey Tryggvadottir

  4. Department of Surgery, University Hospital, 101 Reykjavik, Iceland.

    • Thorvaldur Jonsson

  5. Steno Diabetes Center, DK-2820 Copenhagen, Denmark.

    • Knut Borch-Johnsen
    • , Torben Hansen
    • , Gitte Andersen
    •  & Oluf Pedersen

  6. Faculty of Health Science, University of Aarhus, DK-8000 Aarhus, Denmark.

    • Knut Borch-Johnsen
    •  & Oluf Pedersen

  7. Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark.

    • Torben Jorgensen

  8. Comprehensive Cancer Centre East, 6500 HB Nijmegen, The Netherlands.

    • Katja K Aben
    •  & Lambertus A Kiemeney

  9. Radboud University Nijmegen Department of Urology, 6500 HB Nijmegen, The Netherlands.

    • J Alfred Witjes
    •  & Lambertus A Kiemeney

  10. Radboud University Nijmegen Department of Clinical Chemistry, 6500 HB Nijmegen, The Netherlands.

    • Dorine W Swinkels

  11. Radboud University Nijmegen Department of Endocrinology, 6500 HB Nijmegen, The Netherlands.

    • Martin den Heijer

  12. Radboud University Nijmegen Department of Genetics, 6500 HB Nijmegen, The Netherlands.

    • Barbara Franke

  13. Radboud University Nijmegen Medical Center Department of Epidemiology & Biostatistics, 6500 HB Nijmegen, The Netherlands.

    • Andre L M Verbeek
    •  & Lambertus A Kiemeney

  14. The Johns Hopkins Sibling and Family Heart Study, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.

    • Diane M Becker
    • , Lisa R Yanek
    •  & Lewis C Becker

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Contributions

D.F.G., G.B.W., G.T., H.S., P.S. and K.S. wrote the first draft of the paper. G.B.W., S.T., E.J.O., G.H.O., T. Jonsson, L.T. and T.R. participated in the collection of Icelandic data. V.S., K.B.-J., T.H., G.A., T. Jorgensen and O.P. collected the Danish data. K.K.A., J.A.W., D.W.S., M.H., B.F., A.L.M.V. and L.A.K. collected the Dutch data. D.M.B., L.R.Y. and L.C.B. collected the US data. D.F.G., G.T., H.S., B.V.H., P.Z., P.S., A.G., S.S. and A.I. analyzed the data. G.B.W., A.H. and U.T. carried out the genotyping. D.F.G., J.G., A.K., U.T. and K.S. planned and supervised the work. All authors contributed to the final version of the paper.

Competing interests

The authors from Decode Genetics Inc. own stocks and stock options in the company.

Corresponding authors

Correspondence to Daniel F Gudbjartsson or Kari Stefansson.

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DOI

https://doi.org/10.1038/ng.122

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