TY - JOUR
T1 - Genetic regulation of the placental transcriptome underlies birth weight and risk of childhood obesity
AU - Peng, Shouneng
AU - Deyssenroth, Maya A.
AU - Di Narzo, Antonio F.
AU - Cheng, Haoxiang
AU - Zhang, Zhongyang
AU - Lambertini, Luca
AU - Rusualepp, Arno
AU - Kovacic, Jason C.
AU - Bjorkegren, Johan L.M.
AU - Marsit, Carmen J.
AU - Chen, Jia
AU - Hao, Ke
N1 - Publisher Copyright:
© 2018 Peng et al. http://creativecommons.org/licenses/by/4.0/.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85059518826&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1007799
DO - 10.1371/journal.pgen.1007799
M3 - Article
C2 - 30596636
AN - SCOPUS:85059518826
SN - 1553-7390
VL - 14
JO - PLoS Genetics
JF - PLoS Genetics
IS - 12
M1 - e1007799
ER -
