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DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood

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Listed:
  • Prachand Issarapu

    (CSIR-Centre for Cellular and Molecular Biology
    MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine (LSHTM))

  • Manisha Arumalla

    (CSIR-Centre for Cellular and Molecular Biology)

  • Hannah R. Elliott

    (MRC Integrative Epidemiology Unit at the University of Bristol
    Bristol Medical School, University of Bristol)

  • Suraj S. Nongmaithem

    (CSIR-Centre for Cellular and Molecular Biology)

  • Alagu Sankareswaran

    (CSIR-Centre for Cellular and Molecular Biology
    AcSIR)

  • Modupeh Betts

    (MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine (LSHTM))

  • Sara Sajjadi

    (CSIR-Centre for Cellular and Molecular Biology
    AcSIR)

  • Noah J. Kessler

    (University of Cambridge)

  • Swati Bayyana

    (CSIR-Centre for Cellular and Molecular Biology
    AcSIR)

  • Sohail R. Mansuri

    (CSIR-Centre for Cellular and Molecular Biology
    AcSIR)

  • Maria Derakhshan

    (MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine (LSHTM))

  • G. V. Krishnaveni

    (CSI Holdsworth Memorial Hospital)

  • Smeeta Shrestha

    (CSIR-Centre for Cellular and Molecular Biology)

  • Kalyanaraman Kumaran

    (CSI Holdsworth Memorial Hospital
    University of Southampton)

  • Chiara Gravio

    (Vanderbilt University Medical Center)

  • Sirazul A. Sahariah

    (Centre for the Study of Social Change)

  • Eleanor Sanderson

    (MRC Integrative Epidemiology Unit at the University of Bristol
    Bristol Medical School, University of Bristol)

  • Caroline L. Relton

    (MRC Integrative Epidemiology Unit at the University of Bristol
    Bristol Medical School, University of Bristol)

  • Kate A. Ward

    (MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine (LSHTM)
    King’s College London)

  • Sophie E. Moore

    (MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine (LSHTM)
    King’s College London)

  • Andrew M. Prentice

    (MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine (LSHTM))

  • Karen A. Lillycrop

    (University of Southampton
    University of Southampton)

  • Caroline H. D. Fall

    (University of Southampton)

  • Matt J. Silver

    (MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine (LSHTM))

  • Giriraj R. Chandak

    (CSIR-Centre for Cellular and Molecular Biology
    AcSIR)

Abstract

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)—height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children’s SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

Suggested Citation

  • Prachand Issarapu & Manisha Arumalla & Hannah R. Elliott & Suraj S. Nongmaithem & Alagu Sankareswaran & Modupeh Betts & Sara Sajjadi & Noah J. Kessler & Swati Bayyana & Sohail R. Mansuri & Maria Derak, 2023. "DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40607-0
    DOI: 10.1038/s41467-023-40607-0
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    References listed on IDEAS

    as
    1. Dae-Chul Cho & Holly J. Brennan & Rachelle W. Johnson & Ingrid J. Poulton & Jonathan H. Gooi & Brett A. Tonkin & Narelle E. McGregor & Emma C. Walker & David J. Handelsman & T. J. Martin & Natalie A. , 2017. "Bone corticalization requires local SOCS3 activity and is promoted by androgen action via interleukin-6," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
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    4. Tom P. Fleming & Congshan Sun & Oleg Denisenko & Laura Caetano & Anan Aljahdali & Joanna M. Gould & Pooja Khurana, 2021. "Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk," IJERPH, MDPI, vol. 18(17), pages 1-19, September.
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