Abstract
Expression quantitative trait loci in placenta tissues from the national children’s study reveal developmental origins of human complex diseases
Placenta (Eastbourne), Vol.35(9), pp.A49-A49
09/2014
DOI: 10.1016/j.placenta.2014.06.161
Abstract
Background: The placenta is a key organ in fetal growth and development. It controls fetal access to nutrients, hormones, and gestational challenges, affects development of multiple systems, and profoundly influences postnatal disease susceptibility. Nevertheless, understanding of the placental gene expression profile and its genetic control is incomplete.
Methods: As part of National Children’s Study Formative Research Project LOI2-BIO-18, the transcriptome of 171 placenta tissues was profiled by high depth RNA sequencing (Illumina High-Seq 2500), and linked to fetal genotype assessed by high density single nucleotide polymorphism (SNP) array (Illumina OmniExpressExome). We derived expression quantitative trait loci (eQTLs) that were associated with suspected disease causing loci (NHGRI Genome Wide Association Studies [GWAS] catalog).
Results: Focusing on well-characterized genes (UCSC Genome Browser annotation data), we discovered 3,348 cis- and 77 trans-eQTLs at 10% FDR, a large fraction of which reside in regulatory elements (ENCODE Project). Among ∼11,000 known disease loci of genome-wide significance, 1,525 were placenta eSNPs (25.2 fold enrichment, p=5.6e-141). In particular, GWAS findings of several immunological (e.g, asthma, inflammatory bowel disease, and type I diabetes), psychiatric (e.g, bipolar disorder and schizophrenia), and developmental (e.g., height and pubertal anthropometrics) disorders strongly overlap with placenta eQTLs. Of 62 published asthma GWAS SNPs, 28 are eSNPs found in placentae (82.1 fold enrichment, p=9.8e-49). Of 24 GWAS loci linked to pubertal anthropometrics, 20 are placental eSNPs (151.5 fold enrichment, p=6.9e-45).
Conclusion: Placentae have very active gene expression profiles. A large number of eQTLs profoundly influence transcription. Many overlap with GWAS loci underlying complex diseases, suggesting these genetic variants may modify disease susceptibility during early development. Further, the GWAS loci have substantial effect sizes influencing placental gene expression. Immune, psychiatric, and developmental disease genetic loci showed particularly high overlap with placenta eQTLs, suggesting potential fetal origins in these disorders.
Details
- Title: Subtitle
- Expression quantitative trait loci in placenta tissues from the national children’s study reveal developmental origins of human complex diseases
- Creators
- Ke Hao - Icahn School of Medicine at Mount SinaiAntonio Di Narzo - Icahn School of Medicine at Mount SinaiJia Chen - Icahn School of Medicine at Mount SinaiJoel Dudley - Icahn School of Medicine at Mount SinaiNina Horowitz - Icahn School of Medicine at Mount SinaiEric Schadt - Icahn School of Medicine at Mount SinaiLuca Lambertini - Icahn School of Medicine at Mount SinaiPhilip Landrigan - Icahn School of Medicine at Mount SinaiKjersti Aagaard - Baylor College of MedicineCharlotte Hobbs - University of Arkansas, College of Medicine, Little Rock, AR, USAMichael Varner - University of UtahNancy Dole - University of North Carolina, Chapel Hill, NC, USAJennifer Culhane - Children's Hospital of PhiladelphiaJames Swanson - University of California, IrvineNatalie Thiex - South Dakota State UniversityJeffrey Murray - University of IowaJohn Moye - National Children’s Study, National Institutes of Health, Bethesda, MD, USACarol Kasten - United States Food and Drug AdministrationChristopher Stodgell - University of RochesterRichard Miller - University of Rochester
- Resource Type
- Abstract
- Publication Details
- Placenta (Eastbourne), Vol.35(9), pp.A49-A49
- DOI
- 10.1016/j.placenta.2014.06.161
- ISSN
- 0143-4004
- eISSN
- 1532-3102
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 09/2014
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9985075323902771
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