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Genetic regulation of the placental transcriptome underlies birth weight and risk of childhood obesity
- Source :
- PLoS Genetics, Vol 14, Iss 12, p e1007799 (2018), PLoS Genetics
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
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.<br />Author summary Genetic studies (e.g GWAS) revealed substantial heritability on birth weight (BW), childhood obesity (CO) and childhood body mass index (CBMI), however, the etiological mechanisms and relevant tissue(s) underlying these traits/conditions are not clear. We incorporated the data from largest GWASes to date and placenta expressional quantitative trait loci (eQTL) that have been newly published, and showed the variants 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 in 7 adult tissues such as adipose and liver, only eQTLs in the placenta were found to contribute significantly not only to anthropometry outcomes at birth (BW) but also to childhood phenotypes (CO/CBMI). Further, we employed COLOC and MetaXcan analyses and identified placenta transcripts potential mediate the genetic effect of BW/CO/CBMI GWAS loci. In summary, our study strongly supports a key role for the placenta in determining BW, CO and CMBI at the molecular level, and pinpointed genes whose expression levels in placenta potentially influences BW and CO risk.
- Subjects :
- Male
0301 basic medicine
Pediatric Obesity
Cancer Research
Physiology
Placenta
Gene Expression
Genome-wide association study
QH426-470
030105 genetics & heredity
Bioinformatics
Body Mass Index
Fetal Development
Transcriptome
Mathematical and Statistical Techniques
Pregnancy
Risk Factors
Medicine and Health Sciences
Birth Weight
Child
Genetics (clinical)
2. Zero hunger
Statistics
Genomics
Metaanalysis
medicine.anatomical_structure
Physiological Parameters
Child, Preschool
Physical Sciences
Female
Research Article
Childhood Obesity
Birth weight
Quantitative Trait Loci
Biology
Research and Analysis Methods
Polymorphism, Single Nucleotide
Childhood obesity
03 medical and health sciences
Genome-Wide Association Studies
Genetics
medicine
Humans
Obesity
Statistical Methods
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Fetus
Body Weight
Infant, Newborn
Case-control study
Biology and Life Sciences
Computational Biology
Human Genetics
Genome Analysis
medicine.disease
Human genetics
030104 developmental biology
Gene Expression Regulation
Genetic Loci
Case-Control Studies
Mathematics
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15537404
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- PLOS Genetics
- Accession number :
- edsair.doi.dedup.....ae729cc29c93af3818e3d87d6db02a7b