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Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth

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  • Xiumei Hong

    (Center on the Early Life Origins of Disease, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health)

  • Ke Hao

    (Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Hongkai Ji

    (Johns Hopkins University Bloomberg School of Public Health Baltimore)

  • Shouneng Peng

    (Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Ben Sherwood

    (Johns Hopkins University Bloomberg School of Public Health Baltimore)

  • Antonio Di Narzo

    (Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Hui-Ju Tsai

    (Feinberg School of Medicine, Northwestern University
    Institute of Population Health Sciences, National Health Research Institutes)

  • Xin Liu

    (Feinberg School of Medicine, Northwestern University
    Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences)

  • Irina Burd

    (Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine)

  • Guoying Wang

    (Center on the Early Life Origins of Disease, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health)

  • Yuelong Ji

    (Center on the Early Life Origins of Disease, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health)

  • Deanna Caruso

    (Center on the Early Life Origins of Disease, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health)

  • Guangyun Mao

    (Center on the Early Life Origins of Disease, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health)

  • Tami R. Bartell

    (Mary Ann & J. Milburn Smith Child Health Research Program, Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago)

  • Zhongyang Zhang

    (Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Colleen Pearson

    (Boston University School of Medicine and Boston Medical Center)

  • Linda Heffner

    (Boston University School of Medicine)

  • Sandra Cerda

    (Boston Medical Center, Boston University School of Medicine)

  • Terri H. Beaty

    (Johns Hopkins University Bloomberg School of Public Health)

  • M. Daniele Fallin

    (Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University Bloomberg School of Public Health)

  • Aviva Lee-Parritz

    (Boston University School of Medicine)

  • Barry Zuckerman

    (Boston University School of Medicine and Boston Medical Center)

  • Daniel E. Weeks

    (Graduate School of Public Health, University of Pittsburgh)

  • Xiaobin Wang

    (Center on the Early Life Origins of Disease, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health
    Johns Hopkins University School of Medicine)

Abstract

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such ‘missing heritability’ may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10−8; empirical PG × E=1.2 × 10−8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10−9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.

Suggested Citation

  • Xiumei Hong & Ke Hao & Hongkai Ji & Shouneng Peng & Ben Sherwood & Antonio Di Narzo & Hui-Ju Tsai & Xin Liu & Irina Burd & Guoying Wang & Yuelong Ji & Deanna Caruso & Guangyun Mao & Tami R. Bartell & , 2017. "Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth," Nature Communications, Nature, vol. 8(1), pages 1-10, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15608
    DOI: 10.1038/ncomms15608
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