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

Autor: Peng S; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Deyssenroth MA; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Di Narzo AF; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Cheng H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Zhang Z; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Lambertini L; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Ruusalepp A; Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia., Kovacic JC; Cardiovascular Research Centre, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Bjorkegren JLM; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden., Marsit CJ; Environmental Health at Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America., Chen J; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Hao K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.; College of Environmental Science and Engineering, Tongji University, Shanghai, China.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2018 Dec 31; Vol. 14 (12), pp. e1007799. Date of Electronic Publication: 2018 Dec 31 (Print Publication: 2018).
DOI: 10.1371/journal.pgen.1007799
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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