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Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank.

ABSTRACT: Background:To date, 60 genetic variants have been robustly associated with birthweight. It is unclear whether these associations represent the effect of an individual's own genotype on their birthweight, their mother's genotype, or both. Methods:We demonstrate how structural equation modelling (SEM) can be used to estimate both maternal and fetal effects when phenotype information is present for individuals in two generations and genotype information is available on the older individual. We conduct an extensive simulation study to assess the bias, power and type 1 error rates of the SEM and also apply the SEM to birthweight data in the UK Biobank study. Results:Unlike simple regression models, our approach is unbiased when there is both a maternal and a fetal effect. The method can be used when either the individual's own phenotype or the phenotype of their offspring is not available, and allows the inclusion of summary statistics from additional cohorts where raw data cannot be shared. We show that the type 1 error rate of the method is appropriate, and that there is substantial statistical power to detect a genetic variant that has a moderate effect on the phenotype and reasonable power to detect whether it is a fetal and/or a maternal effect. We also identify a subset of birthweight-associated single nucleotide polymorphisms (SNPs) that have opposing maternal and fetal effects in the UK Biobank. Conclusions:Our results show that SEM can be used to estimate parameters that would be difficult to quantify using simple statistical methods alone.

SUBMITTER: Warrington NM

PROVIDER: S-EPMC6124616 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank.

Warrington Nicole M NM Freathy Rachel M RM Neale Michael C MC Evans David M DM

International journal of epidemiology 20180801 4

<h4>Background</h4>To date, 60 genetic variants have been robustly associated with birthweight. It is unclear whether these associations represent the effect of an individual's own genotype on their birthweight, their mother's genotype, or both.<h4>Methods</h4>We demonstrate how structural equation modelling (SEM) can be used to estimate both maternal and fetal effects when phenotype information is present for individuals in two generations and genotype information is available on the older indi ...[more]

PMID: 29447406

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Project description:BackgroundThe UK Biobank study provides a unique opportunity to study the causes and consequences of disease. We aimed to use the UK Biobank data to study the well-established, but poorly understood, association between low birthweight and type 2 diabetes.MethodsWe used logistic regression to calculate the odds ratio for participants' risk of type 2 diabetes given a one standard deviation increase in birthweight. To test for an association between parental diabetes and birthweight, we performed linear regression of self-reported parental diabetes status against birthweight. We performed path and mediation analyses to test the hypothesis that birthweight partly mediates the association between parental diabetes and participant type 2 diabetes status.ResultsOf the UK Biobank participants, 277 261 reported their birthweight. Of 257 715 individuals of White ethnicity and singleton pregnancies, 6576 had type 2 diabetes, 19 478 reported maternal diabetes (but not paternal), 20 057 reported paternal diabetes (but not maternal) and 2754 participants reported both parents as having diabetes. Lower birthweight was associated with type 2 diabetes in the UK Biobank participants. A one kilogram increase in birthweight was associated with a lower risk of type 2 diabetes (odds ratio: 0.74; 95% CI: 0.71, 0.76; P = 2 × 10(-57)). Paternal diabetes was associated with lower birthweight (45 g lower; 95% CI: 36, 54; P = 2 × 10(-23)) relative to individuals with no parental diabetes. Maternal diabetes was associated with higher birthweight (59 g increase; 95% CI: 50, 68; P = 3 × 10(-37)). Participants' lower birthweight was a mediator of the association between reported paternal diabetes and participants' type 2 diabetes status, explaining 1.1% of the association, and participants' higher birthweight was a mediator of the association between reported maternal diabetes and participants' type 2 diabetes status, explaining 1.2% of the association.ConclusionsData from the UK Biobank provides the strongest evidence by far that paternal diabetes is associated with lower birthweight, whereas maternal diabetes is associated with increased birthweight. Our findings with paternal diabetes are consistent with a role for the same genetic factors influencing foetal growth and type 2 diabetes.

Project description:ObjectiveThe study aims to determine the magnitude and factors that affect maternal death in different settings.Design, setting and analysisA review of national maternal death surveillance data was conducted. The data were obtained through medical record review and verbal autopsies of each death. Generalised structural equation modelling was employed to simultaneously examine the relationships among exogenous, mediating (urban/rural residence) and endogenous variables.OutcomeMagnitude and factors related to the location of maternal death.ParticipantsA total of 4316 maternal deaths were reviewed from 2013 to 2020.ResultsFacility death constitutes 69.0% of maternal deaths in the reporting period followed by home death and death while in transit, each contributing to 17.0% and 13.6% of maternal deaths, respectively. Educational status has a positive direct effect on death occurring at home (β=0.42, 95% CI 0.22 to 0.66), obstetric haemorrhage has a direct positive effect on deaths occurring at home (β=0.41, 95% CI 0.04 to 0.80) and death in transit (β=0.68, 95% CI 0.48 to 0.87), while it has a direct negative effect on death occurring at a health facility (β=-0.60, 95% CI -0.77 to -0.44). Moreover, unanticipated management of complication has a positive direct (β=0.99, 95% CI 0.34 to 1.63), indirect (β=0.05, 95% CI 0.04 to 0.07) and total (β=1.04, 95% CI 0.38 to 1.70) effect on facility death. Residence is a mediator variable and is associated with all places of death. It has a connection with facility death (β=-0.70, 95% CI -0.95 to -0.46), death during transit (β=0.51, 95% CI 0.20 to 0.83) and death at home (β=0.85, 95% CI 0.54 to 1.17).ConclusionAlmost 7 in 10 maternal deaths occurred at the health facility. Sociodemographic factors, medical causes of death and non-medical causes of death mediated by residence were factors associated with the place of death. Thus, factors related to the place of death should be considered as an area of intervention to mitigate preventable maternal death that occurred in different settings.

Dataset Information

Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank.

Publications

Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank.

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