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

• Published in: PLoS genetics 2018-12, Vol.14 (12), p.e1007799
• Main Authors: Peng, Shouneng, Deyssenroth, Maya A, Di Narzo, Antonio F, Cheng, Haoxiang, Zhang, Zhongyang, Lambertini, Luca, Ruusalepp, Arno, Kovacic, Jason C, Bjorkegren, Johan L M, Marsit, Carmen J, Chen, Jia, Hao, Ke
• Format: Article
• Language: English
• Subjects: Analysis; Anthropometry; Biology; Biology and Life Sciences; Birth weight; Birth Weight - genetics; Body Mass Index; Body size; Cardiovascular diseases; Case-Control Studies; Child; Child, Preschool; Childhood; Childhood obesity; Children; Diabetes; Disease; Environmental health; Female; Fetal Development - genetics; Fetuses; Gene expression; Gene Expression Regulation; Genetic aspects; Genetic regulation; Genetics; Genome-Wide Association Study; Genomes; Genomics; Health aspects; Humans; Infant, Newborn; Male; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Metabolism; Obesity; Pediatric Obesity - genetics; Pediatric Obesity - pathology; Phenotypes; Physical Sciences; Placenta; Placenta - metabolism; Polymorphism, Single Nucleotide; Pregnancy; Public health; Quantitative Trait Loci; Research and Analysis Methods; Risk Factors; Studies; Therapeutic applications; Transcription; Transcriptome
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1007799

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.