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Genotype-environment interaction on human cognitive function conditioned on the status of breastfeeding and maternal smoking around birth.

ABSTRACT: We estimated genotype by environment interaction (G?×?E) on later cognitive performance and educational attainment across four unique environments, i.e. 1) breastfed without maternal smoking, 2) breastfed with maternal smoking, 3) non-breastfed without maternal smoking and 4) non-breastfed with maternal smoking, using a novel design and statistical approach that was facilitated by the availability of datasets with the genome-wide single nucleotide polymorphisms (SNPs). There was significant G?×?E for both fluid intelligence (p-value?=?1.0E-03) and educational attainment (p-value?=?8.3E-05) when comparing genetic effects in the group of individuals who were breastfed without maternal smoking with those not breastfed without maternal smoking. There was also significant G?×?E for fluid intelligence (p-value?=?3.9E-05) when comparing the group of individuals who were breastfed with maternal smoking with those not breastfed without maternal smoking. Genome-wide significant SNPs were different between different environmental groups. Genomic prediction accuracies were significantly higher when using the target and discovery sample from the same environmental group than when using those from the different environmental groups. This finding demonstrates G?×?E has important implications for future studies on the genetic architecture, genome-wide association studies and genomic predictions.

SUBMITTER: Lee SH

PROVIDER: S-EPMC5519601 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Genotype-environment interaction on human cognitive function conditioned on the status of breastfeeding and maternal smoking around birth.

Lee S Hong SH Weerasinghe W M Shalanee P WMSP van der Werf Julius H J JHJ

Scientific reports 20170720 1

We estimated genotype by environment interaction (G × E) on later cognitive performance and educational attainment across four unique environments, i.e. 1) breastfed without maternal smoking, 2) breastfed with maternal smoking, 3) non-breastfed without maternal smoking and 4) non-breastfed with maternal smoking, using a novel design and statistical approach that was facilitated by the availability of datasets with the genome-wide single nucleotide polymorphisms (SNPs). There was significant G × ...[more]

PMID: 28729621

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Project description:ObjectiveThe influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis (AC), and atopic dermatitis (AD) remains incompletely understood. We performed a rigorous mendelian randomization (MR) study to obtain the unconfounded association between MSAB and allergic diseases in offspring with and without adjustment for the effect of breastfeeding.MethodsUtilizing publicly available information of MSAB, breastfeeding, CA, AR, AC, and AD from large-scale genome-wide association studies (GWAS), we performed a two-sample mendelian randomization (TSMR) analysis to assess the respective causal relationship of MSAB and breastfeeding to allergic diseases in offspring. To get a reliable conclusion, MR Egger regression, weighted median, and inverse variance weighted (IVW) were employed to estimate the causality, with IVW as the primary analysis. Multivariate MR (MVMR) analysis was used to assess the effect of MSAB on allergic diseases after adjusting for breastfeeding's impact. Sensitivity analysis was conducted using the Cochran Q test, MR-Egger, and leave-one-out approaches to ensure the reliability and stability of results.ResultsThe TSMR analysis demonstrated MSAB increased the risks of CA (PIVW = 0.013, OR: 1.018, 95%CI: 1.004 to 1.033) and AD (PIVW = 0.006, OR: 8.293, 95%CI: 1.815 to 37.884) in offspring. Conversely, breastfeeding decreased the risk of CA (PIVW <0.001, OR: 0.946, 95%CI: 0.918 to 0.974). MSAB still increased the risks of CA (P = 0.0497, OR: 1.013, 95%CI: 1.000017 to 1.026) and AD (P = 0.003, OR: 13.800, 95%CI: 2.490 to 269.246) after adjusting for breastfeeding. We observed no strong indication of a negative causality between MSAB and AC and AR.ConclusionOur findings provided robust evidence of the adverse effects of MSAB on offspring. We emphasized the urgency of smoking cessation around birth and the importance of breastfeeding even in smoking mothers.

Project description:ImportanceCigarette smoking during pregnancy increases the risk of preterm birth, low birth weight, and infant mortality.ObjectiveTo assess the probability of preterm birth among expectant mothers who smoked cigarettes before pregnancy and quit smoking at the start or during pregnancy.Design, setting, and participantsThis cross-sectional study analyzed information provided on live birth certificates from 2011 through 2017 that were obtained from US states that implemented the 2003 revision of the US live birth certificate. In total, 25?233?503 expectant mothers who delivered live neonates and had known prepregnancy and trimester-specific cigarette smoking frequency were included in the analyses.ExposuresCigarette smoking frequency (1-9, 10-19, and ?20 cigarettes per day) 3 months prior to pregnancy and for each trimester during pregnancy.Main outcomes and measuresCigarette smoking cessation throughout pregnancy, after the first trimester, after the second trimester, and during the third trimester irrespective of first and second trimester smoking. Probability of preterm birth (<37 weeks' gestation).ResultsOf 25?233?503 expectant mothers who delivered live neonates between 2011 and 2017, the modal age at delivery was 25 to 29 years; 52.9% were non-Hispanic white, 23.6% were Hispanic, and 14.2% were non-Hispanic black women; 22?600?196 mothers did not smoke during the 3 months prior to pregnancy, and 2?633?307 smoked during the 3 months prior to pregnancy. The proportion of prepregnancy smokers who quit throughout pregnancy was 24.3% in 2011 and 24.6% in 2017. The proportion of prepregnancy smokers who quit during the third trimester was 39.5% in 2011 and 39.7% in 2017. High-frequency cigarette smoking often occurred among expectant mothers who smoked during pregnancy (eg, 46.9% of third-trimester smokers smoked ?10 cigarettes per day in 2017). The probability of preterm birth decreased more the earlier smoking cessation occurred in pregnancy. For example, the probability of preterm birth was 9.8% (95% CI, 9.7%-10.0%) among 25- to 29-year-old, non-Hispanic white, primigravida and primiparous expectant mothers (ie, pregnant for the first time and not yet delivered) who smoked 1 to 9 cigarettes per day prior to pregnancy and maintained this frequency throughout their pregnancy. The probability of preterm birth was 9.0% (95% CI, 8.8%-9.1%) if smoking cessation occurred at the start of the second trimester (an 8.9% relative decrease), and 7.8% (95% CI, 7.7%-8.0%) if cessation occurred at the start of pregnancy (a 20.3% relative decrease).Conclusions and relevanceQuitting smoking-and quitting early in pregnancy-was associated with reduced risk of preterm birth even for high-frequency cigarette smokers.

Project description:IntroductionThere has been rapid growth in research exploring gene-environment interaction (G×E) contributing to smoking behaviors. Yet, no systematic review exists to date.MethodsThis article aims to review evidence on the contribution of G×E to the risk of smoking. Through a search of electronic databases (ie, Google Scholar, PubMed, ScienceDirect, and Elsevier) up until May 2014, 16 studies of G×E focused on smoking behaviors were identified. These studies were compared in terms of: research design and sample studied, measure of smoking behavior and environments used, genes explored, and G×E in relation to these factors.ResultsThirteen of 16 studies (81.2%) found at least one significant G×E association. Wide variation in analytic methods was found across studies, especially with respect to the phenotypes of interest, environmental measures used, and tests conducted to estimate G×E. Heterogeneity across studies made it difficult to compare findings and evaluate the strength of evidence for G×E.ConclusionsG×E research on smoking contains studies that are methodologically different, making it difficult to assess the current state of the evidence. To decrease heterogeneity, we offer recommendations related to: (1) choice of measurement for environmental variables, (2) testing and reporting of main and interaction effects, (3) treatment of covariates, (4) reporting gene-environment correlation, and (5) conducting sensitivity analyses and checking for scaling artifacts. Continued study is needed to identify mechanisms by which genes and environmental factors combine to influence smoking behaviors.ImplicationsNo comprehensive review of G×E studies of smoking behavior has previously been published. The present article seeks to fill this gap by providing a comprehensive review of: how G×E has been defined, how twin and molecular genetic methodologies have been used to test for G×E, and which genes and environmental factors are associated with smoking behaviors. Variations in methodological approaches make it difficult to interpret and summarize findings, so recommendations for future research are provided as a means to more easily compare and replicate findings across studies.

Project description:ObjectiveThe objective of this study was to examine associations of mother and infant salivary cortisol, measured three times over the course of a day, and assess whether these varied by breastfeeding status.MethodsWe conducted a cross-sectional study of 54 mothers and their infants aged 4-11 months. Mothers collected their own saliva and that of their infants upon awakening, 30min after waking and at bedtime. Breastfeeding status was reported by mothers and cortisol level was measured in saliva in μg/dl using standard techniques. We used generalized linear models to evaluate relationships between maternal and infant cortisol levels, and assessed whether the relationship differed by breastfeeding status: formula only compared to partial and full breastfeeding, adjusting for infant sex, race, age, maternal education, and family income.ResultsThirty-four infants received formula only and 20 were either partially or fully breastfed. Breastfeeding was associated with higher household income, higher maternal education, and white race. Cortisol levels were higher among breastfed infants at all three time points. After adjustment, maternal cortisol levels were related with infant cortisol at bedtime only (regression estimate 0.06; 95% CI: 0.10, 1.1; p=0.02). The adjusted association between bedtime maternal and infant cortisol was stronger among breastfeeding dyads than among formula-feeding dyads (regression estimate 1.0; 95% CI: 0.1, 2.0; p=0.04 vs. 0.6; CI: -0.1, 1.3; p=0.10). In addition, we assessed the influence of maternal education and household income in our adjusted model; income strengthened the observed association, whereas maternal education did not change the estimate.ConclusionsBreastfeeding mothers and infants had significant correlations for cortisol at bedtime, while formula-feeding dyads did not. These data suggest that several factors may contribute to cortisol synchrony observed in mother/infant dyads, including the transfer of cortisol in human milk, physical interaction such as skin-to-skin contact, and shared environment. In addition, our findings support household income as a possible contributor.

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Genotype-environment interaction on human cognitive function conditioned on the status of breastfeeding and maternal smoking around birth.

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Genotype-environment interaction on human cognitive function conditioned on the status of breastfeeding and maternal smoking around birth.

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