ORCID Profile
0000-0002-8829-4984
Current Organisation
Centre Hospitalier Universitaire de Sherbrooke
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 04-2023
DOI: 10.1038/S41588-023-01343-9
Abstract: The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration ( n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles ( n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.
Publisher: Oxford University Press (OUP)
Date: 21-07-2017
DOI: 10.1093/HMG/DDX290
Publisher: Springer Science and Business Media LLC
Date: 23-04-2019
DOI: 10.1038/S41467-019-09671-3
Abstract: Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni 1.06 x 10 −7 ). In additional analyses in 7,278 participants, .3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2023
Publisher: Springer Science and Business Media LLC
Date: 09-10-2017
DOI: 10.1038/IJO.2017.248
Publisher: Elsevier BV
Date: 04-1995
DOI: 10.1016/S0002-9149(99)80416-0
Abstract: Amyl nitrite may be used to provoke latent gradients in patients with hypertrophic cardiomyopathy (HC) without significant resting outflow tract gradients, but afterload reduction may not be comparable to a more physiologic stressor such as symptom-limited exercise testing. This study compared the ability of amyl nitrite and exercise testing to provoke outflow tract gradients in 57 patients (40 men and 17 women, mean age +/- SD 49 +/- 16 years) with HC (septal thickness 19 +/- 5 mm, average resting gradient 13 +/- 10 mm Hg) who underwent echocardiography at rest, after amyl nitrite inhalation, and after maximal exercise. No significant gradient (< 50 mm Hg) was induced after either provocation in 26 patients (46%) in 15 patients (26%), inducibility was achieved after both stressors, in 6 (11%) after exercise only, and in 10 (18%) after amyl only. Patients with amyl-induced gradients differed from those in whom gradients were noninducible on the basis of smaller outflow tract dimensions (p < 0.001), larger resting gradients (p < 0.001), and a greater prevalence of "septal bulge" morphology (p = 0.02). Those with exercise-induced gradients were able to attain a greater workload (p = 0.07), have larger resting gradients (p = 0.02), and also tended to have a septal bulge morphology (p < or = 0.01). Although outflow tract obstruction increased to similar levels after amyl nitrite (49 +/- 39 mm Hg) and symptom-limited exercise (47 +/- 39 mm Hg), gradients induced by exercise and amyl correlated poorly (r = 0.54).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Springer Science and Business Media LLC
Date: 10-05-2023
Publisher: Cold Spring Harbor Laboratory
Date: 17-10-2018
DOI: 10.1101/442756
Abstract: Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an in idual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for ex le, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offspring’s later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.
Publisher: Springer Science and Business Media LLC
Date: 02-03-2020
DOI: 10.1186/S13073-020-0716-9
Abstract: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P 1.06 × 10 − 7 , of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
Publisher: Springer Science and Business Media LLC
Date: 05-2019
No related grants have been discovered for Catherine Allard.