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Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth

Author

Listed:
  • Øyvind Helgeland

    (University of Bergen
    Norwegian Institute of Public Health)

  • Marc Vaudel

    (University of Bergen)

  • Petur B. Juliusson

    (University of Bergen
    Haukeland University Hospital
    Norwegian Institute of Public Health)

  • Oddgeir Lingaas Holmen

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology)

  • Julius Juodakis

    (University of Gothenburg)

  • Jonas Bacelis

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Bo Jacobsson

    (Norwegian Institute of Public Health
    University of Gothenburg)

  • Haakon Lindekleiv

    (Department of Community Medicine, UiT The Arctic University of Norway)

  • Kristian Hveem

    (Norwegian University of Science and Technology
    HUNT Research Center)

  • Rolv Terje Lie

    (University of Bergen
    University of Bergen)

  • Gun Peggy Knudsen

    (Norwegian Institute of Public Health)

  • Camilla Stoltenberg

    (University of Bergen
    Norwegian Institute of Public Health)

  • Per Magnus

    (Norwegian Institute of Public Health
    University of Oslo)

  • Jørn V. Sagen

    (University of Bergen
    University of Bergen
    Haukeland University Hospital)

  • Anders Molven

    (University of Bergen
    University of Bergen
    Haukeland University Hospital)

  • Stefan Johansson

    (University of Bergen
    Haukeland University Hospital)

  • Pål Rasmus Njølstad

    (University of Bergen
    Haukeland University Hospital)

Abstract

Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in the leptin receptor (LEPR) locus: no effect at birth, increasing effect in infancy, peaking at 6–12 months (rs2767486, P6m = 2.0 × 10−21, β6m = 0.16 sd-BMI), and little effect after age five. We identify a similar transient effect near the leptin gene (LEP), peaking at 1.5 years (rs10487505, P1.5y = 1.3 × 10−8, β1.5y = 0.079 sd-BMI). Both signals are protein quantitative trait loci for soluble-LEPR and LEP in plasma in adults independent from adult traits mapped to the respective genes, suggesting key roles of common variation in the leptin signaling pathway for healthy infant growth.

Suggested Citation

  • Øyvind Helgeland & Marc Vaudel & Petur B. Juliusson & Oddgeir Lingaas Holmen & Julius Juodakis & Jonas Bacelis & Bo Jacobsson & Haakon Lindekleiv & Kristian Hveem & Rolv Terje Lie & Gun Peggy Knudsen , 2019. "Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12308-0
    DOI: 10.1038/s41467-019-12308-0
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    Cited by:

    1. Fartein Ask Torvik & Espen Moen Eilertsen & Laurie J. Hannigan & Rosa Cheesman & Laurence J. Howe & Per Magnus & Ted Reichborn-Kjennerud & Ole A. Andreassen & Pål R. Njølstad & Alexandra Havdahl & Eiv, 2022. "Modeling assortative mating and genetic similarities between partners, siblings, and in-laws," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Suzanne Vogelezang & Jonathan P Bradfield & Tarunveer S Ahluwalia & John A Curtin & Timo A Lakka & Niels Grarup & Markus Scholz & Peter J van der Most & Claire Monnereau & Evie Stergiakouli & Anni Hei, 2020. "Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits," PLOS Genetics, Public Library of Science, vol. 16(10), pages 1-26, October.

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