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Author Notes:

Email: ke.hao@mssm.edu

Editor: Hae Kyung Im, University of Chicago

Conceptualization: Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Carmen J. Marsit, Jia Chen, Ke Hao.

Data curation: Luca Lambertini, Arno Ruusalepp, Jason C. Kovacic, Johan L. M. Bjorkegren, Carmen J. Marsit, Jia Chen, Ke Hao.

Formal analysis: Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Haoxiang Cheng, Zhongyang Zhang, Carmen J. Marsit, Jia Chen, Ke Hao.

Funding acquisition: Ke Hao.

Investigation: Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Carmen J. Marsit, Jia Chen, Ke Hao.

Methodology: Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Carmen J. Marsit, Jia Chen, Ke Hao.

Project administration: Jia Chen, Ke Hao.

Resources: Luca Lambertini, Arno Ruusalepp, Jason C. Kovacic, Johan L. M. Bjorkegren, Carmen J. Marsit, Jia Chen, Ke Hao.

Supervision: Jia Chen, Ke Hao.

Validation: Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Carmen J. Marsit, Jia Chen, Ke Hao.

Writing – original draft: Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Jason C. Kovacic, Johan L. M. Bjorkegren, Carmen J. Marsit, Jia Chen, Ke Hao.

Writing – review & editing: Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Jason C. Kovacic, Johan L. M. Bjorkegren, Carmen J. Marsit, Jia Chen, Ke Hao.

The authors thank Dr. Claudia Giambartolomei for discussion and guidance on COLOC application and result interpretation.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

KH is partially supported by National Natural Science Foundation of China (Grant No. 21477087, 91643201, 21876134), and by Ministry of Science and Technology of China (Grant No. 2016YFC0206507).

SP, MAD, CM, JC, KH are partially supported by National Institute of Environmental Health Sciences (NIH-NIEHS R01ES022223, R01ES022223-03S1, 1R01ES029212-01).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • GENOME-WIDE ASSOCIATION
  • LD SCORE REGRESSION
  • SUSCEPTIBILITY LOCI
  • METAANALYSIS
  • EPIDEMIOLOGY
  • INTEGRATION
  • GWAS

Genetic regulation of the placental transcriptome underlies birth weight and risk of childhood obesity

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Journal Title:

PLoS Genetics

Volume:

Volume 14, Number 12

Publisher:

, Pages e1007799-e1007799

Type of Work:

Article | Final Publisher PDF

Abstract:

GWAS identified variants associated with birth weight (BW), childhood obesity (CO) and childhood BMI (CBMI), and placenta is a critical organ for fetal development and postnatal health. We examined the role of placental transcriptome and eQTLs in mediating the genetic causes for BW, CO and CBMI, and applied integrative analysis (Colocalization and MetaXcan). GWAS loci associated with BW, CO, and CBMI were substantially enriched for placenta eQTLs (6.76, 4.83 and 2.26 folds, respectively). Importantly, compared to eQTLs of adult tissues, only placental eQTLs contribute significantly to both anthropometry outcomes at birth (BW) and childhood phenotypes (CO/CBMI). Eight, six and one transcripts colocalized with BW, CO and CBMI risk loci, respectively. Our study reveals that placental transcription in utero likely plays a key role in determining postnatal body size, and as such may hold new possibilities for therapeutic interventions to prevent childhood obesity.

Copyright information:

© 2018 Peng et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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