The human placenta exhibits a unique transcriptomic void

Gong, Sungsam; Gaccioli, Francesca; Aye, Irving L.M.H.; Avellino, Giulia; Lawson, Andrew; Harvey, Luke M. R.; Smith, Gordon Cs; Charnock-Jones, D. Stephen

doi:10.1101/2022.07.01.498408

Cited by 3 publications

(3 citation statements)

References 69 publications

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“…This is compatible with the decreasing effects that we observe for many genes (Jiang et al, 2021). On the other hand, we do show that our loci are actively expressed in early-to-mid-gestation placenta, which supports a more persistent role throughout pregnancy, and is also notable as many transcripts are missing in the placenta (Gong et al, 2022). In any case, we expect that follow-up studies can use our results to prioritise the most relevant genes and periods for each gene.…”

Section: Discussionsupporting

confidence: 89%

Time-varying effects are common in genetic control of gestational duration

Juodakis

Ytterberg

Flatley

et al. 2023

Preprint

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Preterm birth is a major burden to neonatal health worldwide, determined in part by genetics. Recently, studies discovered several genes associated with this trait or its continuous equivalent - gestational duration. However, their effect timing, and thus clinical importance, is still unclear. Here, we use genotyping data of 31,000 births from the Norwegian Mother, Father and Child cohort (MoBa) to investigate different models of the genetic pregnancy "clock". We conduct genome-wide association studies using gestational duration or preterm birth, replicating known maternal associations and finding one new foetal variant. We illustrate how the interpretation of these results is complicated by the loss of power when dichotomizing. Using flexible survival models, we resolve this complexity and find that many of the known loci have time-varying effects, often stronger early in pregnancy. The overall polygenic control of birth timing appears to be shared in the term and preterm, but not very preterm periods, and exploratory results suggest involvement of the major histocompatibility complex genes in the latter. These findings show that the known gestational duration loci are clinically relevant, and should help design further experimental studies.

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Section: Discussionsupporting

confidence: 89%

Time-varying effects are common in genetic control of gestational duration

Juodakis

Ytterberg

Flatley

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This is compatible with the decreasing effects that we observe for many genes ( 19 ). On the other hand, we do show that our loci are actively expressed in early-to-mid-gestation placenta, which supports a more persistent role throughout pregnancy and is also notable as many transcripts are missing in the placenta ( 20 ). In any case, we expect that follow-up studies can use our results to prioritize the most relevant genes and periods for each gene.…”

Section: Discussionsupporting

confidence: 72%

Time-varying effects are common in genetic control of gestational duration

Juodakis

Ytterberg

Flatley

et al. 2023

Human Molecular Genetics

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Preterm birth is a major burden to neonatal health worldwide, determined in part by genetics. Recently, studies discovered several genes associated with this trait or its continuous equivalent—gestational duration. However, their effect timing, and thus clinical importance, is still unclear. Here, we use genotyping data of 31 000 births from the Norwegian Mother, Father and Child cohort (MoBa) to investigate different models of the genetic pregnancy ‘clock’. We conduct genome-wide association studies using gestational duration or preterm birth, replicating known maternal associations and finding one new foetal variant. We illustrate how the interpretation of these results is complicated by the loss of power when dichotomizing. Using flexible survival models, we resolve this complexity and find that many of the known loci have time-varying effects, often stronger early in pregnancy. The overall polygenic control of birth timing appears to be shared in the term and preterm, but not very preterm periods, and exploratory results suggest involvement of the major histocompatibility complex genes in the latter. These findings show that the known gestational duration loci are clinically relevant, and should help design further experimental studies.

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“…It has been observed that the placenta has a lower level of DNA methylation when compared to other somatic tissues (Ehrlich et al 1982;Robinson and Price 2015), with hypomethylation concentrated in partially methylated domains (Schroeder et al 2013(Schroeder et al , 2015. The placental transcriptome includes a greater number of genes that are uniquely expressed (Gong et al 2021) and uniquely depleted (Gong et al 2022) than other tissues, perhaps in part owing to the distinctive epigenomic landscape. This landscape includes many imprinted genes, which are expressed predominantly from either the maternal or paternal allele and are a feature of organisms that transfer nutrients directly to their developing offspring (Moore and Haig 1991).…”

Section: Introductionmentioning

confidence: 99%

An allele-resolved nanopore-guided tour of the human placental methylome

Kindlova

Byrne

Kubler

et al. 2023

Preprint

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The placenta is a temporary organ present during pregnancy that is responsible for coordinating all aspects of pregnancy between the mother and fetus. It has a distinct epigenetic, transcriptomic, and mutational landscape with low levels of methylation, high numbers of transcribed loci, and a high mutational burden relative to somatic tissues. We present this landscape through the application of nanopore sequencing technology to provide a more comprehensive picture of female placental genomics and methylomics along with integrated haplotype-resolved transcriptomic analyses across eight trios. Whole genome sequencing of trios allows robust phasing, permitting comprehensive genome-wide investigation of parent-of-origin methylation and transcription. This enhanced view facilitates identifications of many new differentially methylated regions (DMRs), both conserved and differing between individuals, as well as novel imprinted genes including ILDR2 and RASA1 which are potentially important for healthy placental and fetal development.

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The human placenta exhibits a unique transcriptomic void

Cited by 3 publications

References 69 publications

Time-varying effects are common in genetic control of gestational duration

Time-varying effects are common in genetic control of gestational duration

Time-varying effects are common in genetic control of gestational duration

An allele-resolved nanopore-guided tour of the human placental methylome

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