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The influence of maternal pregnancy glucose concentrations on associations between a fetal imprinted gene allele score and offspring size at birth.

ABSTRACT: OBJECTIVE:Previously we found that certain fetal imprinted genes represented as an allele score are associated with maternal pregnancy glucose concentrations. Recently it was reported that fetal polymorphisms with strong associations with birth weight tend to mediate these independently of increases in maternal pregnancy glucose concentrations. We therefore investigated whether potential associations between the fetal allele score and birth weight were related to maternal glucose concentrations in the Cambridge Baby Growth Study. RESULTS:The fetal imprinted gene allele score was positively associated with birth weight (??=?63 (17-109) g/risk allele, ?'?=?0.113, p?=?7.6?×?10-3, n?=?405). This association was partially attenuated by adjusting for maternal glucose concentrations (??=?50 (4-95) g/risk allele, ?'?=?0.089, p?=?0.03, n?=?405). The allele score was also positively associated with risk of being large for gestational age at birth (odds ratio 1.60 (1.19-2.15) per risk allele, p?=?2.1?×?10-3, n?=?660) and negatively associated with risk of being small for gestational age at birth (odds ratio 0.65 (0.44-0.96) per risk allele, p?=?0.03, n?=?660). The large for gestational age at birth association was also partially attenuated by maternal glucose concentrations. These results suggest that associations between the fetal imprinted gene allele score and size at birth are mediated through both glucose-dependent and glucose-independent mechanisms.

SUBMITTER: Petry CJ

PROVIDER: S-EPMC6245772 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The influence of maternal pregnancy glucose concentrations on associations between a fetal imprinted gene allele score and offspring size at birth.

Petry Clive J CJ Ong Ken K KK Hughes Ieuan A IA Acerini Carlo L CL Dunger David B DB

BMC research notes 20181119 1

<h4>Objective</h4>Previously we found that certain fetal imprinted genes represented as an allele score are associated with maternal pregnancy glucose concentrations. Recently it was reported that fetal polymorphisms with strong associations with birth weight tend to mediate these independently of increases in maternal pregnancy glucose concentrations. We therefore investigated whether potential associations between the fetal allele score and birth weight were related to maternal glucose concent ...[more]

PMID: 30454065

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Project description:BackgroundLow birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP.MethodsUsing a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only "vasculature-related" BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity.ResultsWe observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of "vasculature-related" BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation.ConclusionsOur study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.

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The influence of maternal pregnancy glucose concentrations on associations between a fetal imprinted gene allele score and offspring size at birth.

Publications

The influence of maternal pregnancy glucose concentrations on associations between a fetal imprinted gene allele score and offspring size at birth.

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