Expression quantitative trait loci (eQTLs) in human placentas suggest developmental origins of complex diseases.

ABSTRACT: Epidemiologic studies support that at least part of the risk of chronic diseases in childhood and even adulthood may have an in utero origin, and the placenta is a key organ that plays a pivotal role in fetal growth and development. The transcriptomes of 159 human placenta tissues were profiled by genome-wide RNA sequencing (Illumina High-Seq 2500), and linked to fetal genotypes assessed by a high density single nucleotide polymorphism (SNP) genotyping array (Illumina MegaEx). Expression quantitative trait loci (eQTLs) across all annotated transcripts were mapped and examined for enrichment for disease susceptibility loci annotated in the genome-wide association studies (GWAS) catalog. We discovered 3218 cis- and 35 trans-eQTLs at??10% false discovery rate in human placentas. Among the 16?439 known disease loci of genome-wide significance, 835 were placental eSNPs (enrichment fold?=?1.68, P?=?7.41e-42). Stronger effect sizes were observed between GWAS SNPs and gene expression in placentas than what has been reported in other tissues, such as the correlation between asthma risk allele, rs7216389-T and Gasdermin-B (GSDMB) in placenta (r2=27%) versus lung (r2=6%). Finally, our results suggest the placental eQTLs may mediate the function of GWAS loci on postnatal disease susceptibility. Results suggest that transcripts in placenta are under tight genetic control, and that placental gene networks may influence postnatal risk of multiple human diseases lending support for the Developmental Origins of Health and Disease.

SUBMITTER: Peng S 

PROVIDER: S-EPMC5886245 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature