Genetic variation in placental insufficiency: What have we learned over time?

Wang, Li Qing; Fernández-Boyano, Icíar; Robinson, Wendy P.

doi:10.3389/fcell.2022.1038358

Cited by 7 publications

(3 citation statements)

References 204 publications

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“…The clinical outcome of UPD depends on its origin and the chromosome involved. Some UPD events were reported to be associated with FGR, including paternal UPD6 and UPD15 and maternal UPD 6, UPD 7, UPD11, UPD14, UPD15 and UPD20 [7,8,[19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting

Li,

Hao,

Jiang

et al. 2023

Preprint

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Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases. Furthermore, noninvasive prenatal testing results of the 5 patients revealed a high risk of rare autosomal trisomy. Trio-WES showed no copy-number variations (CNVs) or nondisease-causing mutations associated with FGR. Among the 5 women with FGR, two showed gene imprinting, and two exhibited confined placental mosaicism (CPM) by copy number variant sequencing (CNV-seq). The present study showed that in FGR patients with UPD, the detection of imprinted genes and CPM could enhance the genetic diagnosis of FGR.

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Section: Discussionmentioning

confidence: 99%

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting

Li,

Hao,

Jiang

et al. 2023

Preprint

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“…Among others, chronic hypertension and prior PE are well-known risk factors for PE ( Bartsch et al, 2016 ). Placental, maternal, and paternal genetics also significantly contribute to the pathogenesis of PE ( Williams and Broughton Pipkin, 2011 ; Wang et al, 2022 ). The combination of such genetic and environmental factors plays an important role in the development of PE, which is a two-stage process whereby placental dysfunction leads to maternal onset of disease ( Redman et al, 2014 ); several studies have observed PE-associated molecular and histopathological changes in the human placenta, likely reflecting the observed placental dysfunction ( Leavey et al, 2016 ; Benton et al, 2018 ; Wilson et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

eoPred: predicting the placental phenotype of early-onset preeclampsia using public DNA methylation data

Fernández-Boyano,

Inkster,

Yuan

et al. 2023

Front. Genet.

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Background: A growing body of literature has reported molecular and histological changes in the human placenta in association with preeclampsia (PE). Placental DNA methylation (DNAme) and transcriptomic patterns have revealed molecular subgroups of PE that are associated with placental histopathology and clinical phenotypes of the disease. However, the clinical and molecular heterogeneity of PE both across and within subtypes complicates the study of this disease. PE is most strongly associated with placental pathology and adverse fetal and maternal outcomes when it develops early in pregnancy. We focused on placentae from pregnancies affected by preeclampsia that were delivered before 34 weeks of gestation to develop eoPred, a predictor of the DNAme signature associated with the placental phenotype of early-onset preeclampsia (EOPE).Results: Public data from 83 placental samples (HM450K), consisting of 42 EOPE and 41 normotensive preterm birth (nPTB) cases, was used to develop eoPred—a supervised model that relies on a highly discriminative 45 CpG DNAme signature of EOPE in the placenta. The performance of eoPred was assessed using cross-validation (AUC = 0.95) and tested in an independent validation cohort (n = 49, AUC = 0.725). A subset of fetal growth restriction (FGR) and late-PE cases showed a similar DNAme profile at the 45 predictive CpGs, consistent with the overlap in placental pathology between these conditions. The relationship between the EOPE probability generated by eoPred and various phenotypic variables was also assessed, revealing that it is associated with gestational age, and it is not driven by cell composition differences.Conclusion: eoPred relies on a 45-CpG DNAme signature to predict a homogeneous placental phenotype of EOPE in a discrete or continuous manner. Using this classifier should 1) aid in the study of placental insufficiency and improve the consistency of future placental DNAme studies of PE, 2) facilitate identifying the placental phenotype of EOPE in public data sets and 3) importantly, standardize the placental diagnosis of EOPE to allow better cross-cohort comparisons. Lastly, classification of cases with eoPred will be useful for investigating the relationship between placental pathology and genetic or environmental variables.

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“…Among others, chronic hypertension and prior PE are well-known risk factors for PE (Bartsch et al, 2016). Placental, maternal, and paternal genetics also signi cantly contribute to the pathogenesis of PE (Williams and Broughton Pipkin, 2011; Wang et al, 2022). The combination of such genetic and environmental factors plays an important role in the development of PE, which is a two-stage process whereby placental dysfunction leads to maternal onset of disease (Redman et al, 2014); several studies have observed PE-associated molecular and histopathological changes in the human placenta, likely re ecting the observed placental dysfunction (Leavey et al, 2016;Benton et al, 2018;Wilson et al, 2018).…”

mentioning

confidence: 99%

eoPred: Predicting the placental phenotype of early-onset preeclampsia using DNA methylation

Boyano

Inkster

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

Background A growing body of literature has reported molecular and histological changes in the human placenta in association with preeclampsia (PE). Placental DNA methylation (DNAme) and transcriptomic patterns have revealed molecular subgroups of PE that are associated with placental histopathology and clinical phenotypes of the disease. However, the heterogeneity of PE both across and within subtypes, whether defined clinically or molecularly, complicates the study of this disease. PE is most strongly associated with placental pathology and adverse fetal and maternal outcomes when it develops early in pregnancy. We focused on placentae from pregnancies affected by preeclampsia that were delivered before 34 weeks of gestation to develop eoPred, a predictor of the DNAme signature associated with the placental phenotype of early-onset preeclampsia (EOPE). Results Public data from 83 placental samples (HM450K), consisting of 42 EOPE and 41 normotensive preterm birth (nPTB) cases, was used to develop eoPred - a supervised model that relies on a highly discriminative 45 CpG DNAme signature of EOPE in the placenta. The performance of eoPred was assessed using cross-validation (AUC = 0.95) and tested in an independent validation cohort (n = 49, AUC = 0.725). A subset of fetal growth restriction (FGR) and late-PE cases showed a similar DNAme profile at the 45 predictive CpGs, consistent with the overlap in placental pathology between these conditions. The relationship between the EOPE probability generated by eoPred and various phenotypic variables was also assessed, revealing that it is associated with gestational age, and it is not driven by cell composition differences. Conclusions eoPred relies on a 45 CpG DNAme signature to predict EOPE, and it can be used in a discrete or continuous manner. Using this classifier should 1) improve the consistency of future placental DNAme studies of PE and placental insufficiency, 2) facilitate identifying cases of EOPE in public data sets and 3) importantly, standardize the placental diagnosis to allow better cross-cohort comparisons. Lastly, classification of cases with eoPred should be useful for testing associations between placental pathology and genetic or environmental variables.

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Genetic variation in placental insufficiency: What have we learned over time?

Cited by 7 publications

References 204 publications

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting

eoPred: predicting the placental phenotype of early-onset preeclampsia using public DNA methylation data

eoPred: Predicting the placental phenotype of early-onset preeclampsia using DNA methylation

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