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

• Type of Material: Article
• Authors: Shouneng Peng, Icahn School of Medicine at Mount Sinai; Maya A. Deyssenroth, Icahn School of Medicine at Mount Sinai; Antonio F. Di Narzo, Icahn School of Medicine at Mount Sinai; Haoxiang Cheng, Icahn School of Medicine at Mount Sinai; Zhongyang Zhang, Icahn School of Medicine at Mount Sinai; Luca Lambertini, Icahn School of Medicine at Mount Sinai; Arno Rusualepp, Tartu University Hosptial; Jason C. Kovacic, Icahn School of Medicine at Mount Sinai; Johan L. M. Bjorkegren, Icahn School of Medicine at Mount Sinai; Carmen Marsit, Emory University; Jia Chen, Icahn School of Medicine at Mount Sinai; Ke Hao, Icahn School of Medicine at Mount Sinai
• Language: English
• Date: 2018-12-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Peng et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pgen.1007799
• Title of Journal or Parent Work: PLoS Genetics
• ISSN: 1553-7390
• Volume: 14
• Issue: 12
• Start Page: e1007799
• End Page: e1007799
• Grant/Funding Information: 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; Genetics & Heredity; SUSCEPTIBILITY LOCI; EPIDEMIOLOGY; METAANALYSIS; Life Sciences & Biomedicine; GENOME-WIDE ASSOCIATION; GWAS; LD SCORE REGRESSION; INTEGRATION
• Research Categories: Health Sciences, Epidemiology; Biology, Genetics; Health Sciences, Obstetrics and Gynecology

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.