Genetic regulation of the placental transcriptome underlies birth weight and risk of childhood obesity
Genetic regulation of the placental transcriptome underlies birth weight and risk of childhood obesity
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DOI：
10.1371/journal.pgen.1007799
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发表时间：
2018-12
期刊：
影响因子：
4.5
通讯作者：
Shouneng Peng;Maya A. Deyssenroth;Antonio F Di Narzo;Haoxiang Cheng;Zhongyang Zhang;L. Lambertini;A. Ruusalepp;J. Kovacic;Johan L M Bjorkegren;C. Marsit;Jia Chen;K. Hao
中科院分区：
文献类型：
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作者：
Shouneng Peng;Maya A. Deyssenroth;Antonio F Di Narzo;Haoxiang Cheng;Zhongyang Zhang;L. Lambertini;A. Ruusalepp;J. Kovacic;Johan L M Bjorkegren;C. Marsit;Jia Chen;K. Hao
Gwas发现了与出生体重(BW)、儿童肥胖(CO)和儿童BMI(CBMI)相关的变异，胎盘是胎儿发育和出生后健康的关键器官。我们研究了胎盘转录组和eQTL在调节体重、CO和CBMI的遗传原因中的作用，并应用整合分析(共定位和MetaXcan)。与BW、CO和CBMI相关的GWA基因座显著富含胎盘eQTL(分别为6.76、4.83和2.26倍)。重要的是，与成人组织的eQTL相比，只有胎盘eQTL对出生时的人体测量结果(BW)和儿童的表型(CO/CBMI)都有显著影响。8个、6个和1个转录本分别与BW、CO和CBMI风险基因座共定位。我们的研究表明，胎盘在子宫中的转录可能在决定出生后身体大小方面发挥关键作用，因此可能为预防儿童肥胖的治疗干预提供新的可能性。
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.