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

by Shouneng Peng, Maya A. Deyssenroth, Antonio F. Di Narzo, Haoxiang Cheng, Zhongyang Zhang, Luca Lambertini, Arno Rusualepp, Jason C. Kovacic, Johan L. M. Bjorkegren, Carmen J. Marsit, Jia Chen, Ke Hao

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.

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