scholarly journals Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?

2021 ◽  
Author(s):  
Anna E. Bauer ◽  
Christy L. Avery ◽  
Min Shi ◽  
Clarice R. Weinberg ◽  
Andrew F. Olshan ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Maternal Smoking ◽  
Risk Allele ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Maternal Genotype ◽  
Family Based ◽  
Complex Relationships ◽  
Log Linear ◽  
Risk Of Preeclampsia

Objective Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. Study Design We conducted a nested case–control study within the Norwegian Mother, Father and Child Birth Cohort (1999–2008) of 2,596 mother–child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. Results Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). Conclusion Evidence for gene–smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene–environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures. Key Points

scholarly journals Interaction between the DNAH9 gene and early smoke exposure in bronchial hyperresponsiveness

2016 ◽  
Vol 47 (4) ◽  
pp. 1072-1081 ◽  
Author(s):  
Marie-Hélène Dizier ◽  
Rachel Nadif ◽  
Patricia Margaritte-Jeannin ◽  
Sheila J. Barton ◽  
Chloé Sarnowski ◽  
...  
Keyword(s):  
Significant Interaction ◽  
Multiple Testing ◽  
Bronchial Hyperresponsiveness ◽  
Homogeneity Test ◽  
Nucleotide Polymorphisms ◽  
Linear Interaction ◽  
Genome Wide ◽  
Respiratory Cilia ◽  
Family Based ◽  
Log Linear

A previous genome-wide linkage scan of bronchial hyperresponsiveness (BHR) in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families, performed in the presence of a gene×early-life environmental tobacco smoke (ETS) exposure interaction, showed the strongest interaction in the 17p11 region where linkage was detected only among unexposed siblings. Our goal was to conduct fine-scale mapping of 17p11 to identify single nucleotide polymorphisms (SNPs) interacting with ETS that influence BHR.Analyses were performed in 388 French EGEA asthmatic families, using a two-step strategy: 1) selection of SNPs displaying family-based association test (FBAT) association signals (p≤0.01) with BHR in unexposed siblings, and 2) a FBAT homogeneity test between exposed and unexposed siblings plus a robust log-linear interaction test.A single SNP reached the threshold (p≤3×10−3) for significant interaction with ETS using both interaction tests, after accounting for multiple testing. Results were replicated in 253 French-Canadian families, but not in 341 UK families, probably due in part to differences in phenotypic features between datasets.The SNP showing significant interaction with ETS belongs to DNAH9 (dynein, axonemal, heavy chain 9), a promising candidate gene involved in respiratory cilia mobility and associated with primary ciliary dyskinesia, a disease associated with abnormalities of pulmonary function.

Family-based association study of ADHD and genes increasing the risk for smoking behaviours

2012 ◽  
Vol 97 (12) ◽  
pp. 1027-1033 ◽  
Author(s):  
Geeta A Thakur ◽  
Sarojini M Sengupta ◽  
Natalie Grizenko ◽  
Zia Choudhry ◽  
Ridha Joober
Keyword(s):  
Risk Allele ◽  
Clinical Sample ◽  
Smoking Behaviour ◽  
Common Mechanism ◽  
Large Sample Size ◽  
Nucleotide Polymorphisms ◽  
Children With Adhd ◽  
Risk Alleles ◽  
Externalising Behaviours ◽  
Family Based

ObjectiveTo investigate five top single nucleotide polymorphisms (SNPs) located in different genes and loci (CHRNA3, BDNF, DBH and LOC100188947) that were highly associated with different dimensions of smoking behaviour, in relation to attention-deficit hyperactivity disorder (ADHD).DesignCohort study consisting of a clinical sample of children with ADHD.SettingDouglas Institute ADHD Clinic, Montreal, Canada.PatientsFamilies of 454 children with ADHD aged 6–12 years old.InterventionsFamily-based association tests used to study the transmission of risk alleles within these five genetic markers.Main outcome measuresClinical diagnosis of ADHD, and a number of behavioural and neurocognitive phenotypes relevant to the disorder.ResultsOne SNP (rs1329650) from a non-coding RNA (LOC100188947) was significantly associated with overall ADHD diagnosis with the C* risk allele being over-transmitted from parents to children with ADHD (p=0.02). It was also over-transmitted to children with higher scores on Conners’ Parents (p=0.01) and Conners’ Teacher (p=0.002) index scores, and Child Behaviour Checklist withdrawn (p=0.001) and aggressive (p=0.007) behaviours. Children with poorer performances on executive and attention tasks were more likely to inherit the risk allele.ConclusionsThe C* allele of rs1329650 may be increasing the risk for ADHD and smoking behaviour through a common mechanism, possibly externalising behaviours and specific cognitive deficits that manifest as ADHD in childhood and are the gateway to smoking behaviour later in life. This exploratory study illustrates the use of comorbid disorders to investigate ADHD genetics. In spite of its relatively large sample size, replication in future studies is warranted.Trial Registration NumberNCT00483106.

scholarly journals Family-based gene-environment interaction using sequence kernel association test (FGE-SKAT) for complex quantitative traits

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chao-Yu Guo ◽  
Reng-Hong Wang ◽  
Hsin-Chou Yang
Keyword(s):  
Complex Traits ◽  
Association Studies ◽  
Association Test ◽  
Whole Genome Sequence ◽  
Environment Interaction ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Sequence Kernel Association Test ◽  
Gene Environment ◽  
Family Based

AbstractAfter the genome-wide association studies (GWAS) era, whole-genome sequencing is highly engaged in identifying the association of complex traits with rare variations. A score-based variance-component test has been proposed to identify common and rare genetic variants associated with complex traits while quickly adjusting for covariates. Such kernel score statistic allows for familial dependencies and adjusts for random confounding effects. However, the etiology of complex traits may involve the effects of genetic and environmental factors and the complex interactions between genes and the environment. Therefore, in this research, a novel method is proposed to detect gene and gene-environment interactions in a complex family-based association study with various correlated structures. We also developed an R function for the Fast Gene-Environment Sequence Kernel Association Test (FGE-SKAT), which is freely available as supplementary material for easy GWAS implementation to unveil such family-based joint effects. Simulation studies confirmed the validity of the new strategy and the superior statistical power. The FGE-SKAT was applied to the whole genome sequence data provided by Genetic Analysis Workshop 18 (GAW18) and discovered concordant and discordant regions compared to the methods without considering gene by environment interactions.

scholarly journals Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su Yon Jung ◽  
Jeanette C. Papp ◽  
Eric M. Sobel ◽  
Matteo Pellegrini ◽  
Herbert Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Visceral Obesity ◽  
Cumulative Exposure ◽  
Environment Interaction ◽  
Dependent Manner ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Reduction Methods

AbstractMolecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the genome-wide level. With single-nucleotide polymorphisms (SNPs) in the biomarkers and lifestyles together, we further constructed risk profiles to improve predictability for breast cancer. Our earlier genome-wide association gene-environment interaction study used large cohort data from the Women’s Health Initiative Database for Genotypes and Phenotypes Study and identified 88 SNPs associated with CRP and IL-6. For this study, we added an additional 68 SNPs from previous GWA studies, and together with 48 selected lifestyles, evaluated for the association with breast cancer risk via a 2-stage multimodal random survival forest and generalized multifactor dimensionality reduction methods. Overall and in obesity strata (by body mass index, waist, waist-to-hip ratio, exercise, and dietary fat intake), we identified the most predictive genetic and lifestyle variables. Two SNPs (SALL1 rs10521222 and HLA-DQA1 rs9271608) and lifestyles, including alcohol intake, lifetime cumulative exposure to estrogen, and overall and visceral obesity, are the most common and strongest predictive markers for breast cancer across the analyses. The risk profile that combined those variables presented their synergistic effect on the increased breast cancer risk in a gene–lifestyle dose-dependent manner. Our study may contribute to improved predictability for breast cancer and suggest potential interventions for the women with the risk genotypes and lifestyles to reduce their breast cancer risk.

scholarly journals Investigation of gene–environment interactions in relation to tic severity

2021 ◽  
Author(s):  
Mohamed Abdulkadir ◽  
Dongmei Yu ◽  
Lisa Osiecki ◽  
Robert A. King ◽  
Thomas V. Fernandez ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Association Studies ◽  
Autism Spectrum ◽  
Environment Interaction ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Linear Regression Models ◽  
Compulsive Disorder ◽  
Gene Environment ◽  
Tic Severity

AbstractTourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.

scholarly journals Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

2021 ◽  
Vol 18 (12) ◽  
pp. 6597
Author(s):  
Gloria Pérez-Rubio ◽  
Luis Alberto López-Flores ◽  
Ana Paula Cupertino ◽  
Francisco Cartujano-Barrera ◽  
Luz Myriam Reynales-Shigematsu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Quitting Smoking ◽  
Genes Encoding ◽  
Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

scholarly journals Haplotype analysis on correlation between transcription factor 7-like 2 gene polymorphism and breast cancer risk

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Wang ◽  
Xiaojuan Men ◽  
Yongxue Gu ◽  
Huidong Wang ◽  
Zhicai Xu
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Logistic Regression ◽  
Abdominal Obesity ◽  
Haplotype Analysis ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Locus Model ◽  
Gene Environment

Abstract Background Up to now, limited researches focused on the association between transcription factor 7-like 2 gene (TF7L2) gene single nucleotide polymorphisms (SNPs) and breast cancer (BC) risk. The aim of this study was to evaluate the associations between TF7L2 and BC risk in Chinese Han population. Methods Logistic regression model was used to test the correlation between polymorphisms and BC risk. Strength of association was evaluated by odds ratio (OR) and 95% confidence interval (CI). Generalized multifactor dimensionality reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interaction. Results Logistic regression analysis indicated that the BC risk was obviously higher in carriers of rs1225404 polymorphism C allele than that in TT genotype carriers (TC or CC versus TT), adjusted OR (95%CI) =1.40 (1.09–1.72). Additionally, we also discovered that people with rs7903146- T allele had an obviously higher risk of BC than people with CC allele (CT or TT versus CC), adjusted OR (95%CI) =1.44 (1.09–1.82). GMDR model was used to research the effect of interaction among 4 SNPs and environmental factors on BC risk. We discovered an important two-locus model (p = 0.0100) including rs1225404 and abdominal obesity, suggesting a potential gene–environment correlation between rs1225404 and abdominal obesity. In general, the cross-validation consistency of two-locus model was 10 of 10, and the testing accuracy was 0.632. Compared with subjects with normal waist circumference (WC) value and rs1225404 TT genotype, abdominal obese subjects with rs1225404 TC or CC genotype had the highest BC risk. After covariate adjustment, OR (95%CI) was 2.23 (1.62–2.89). Haplotype analysis indicated that haplotype containing rs1225404-T and rs7903146-C alleles were associated with higher BC risk. Conclusions C allele of rs1225404 and T allele of rs7903146, interaction between rs1225404 and abdominal obesity, rs1225404-T and rs7903146-C haplotype were all related to increased BC risk.

scholarly journals Gene–gene and gene-environment interactions on cord blood total IgE in Chinese Han children

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Li Hua ◽  
Quanhua Liu ◽  
Jing Li ◽  
Xianbo Zuo ◽  
Qian Chen ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Cord Blood ◽  
Synergistic Effects ◽  
Gene Interaction ◽  
Independent Effect ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Gene Environment Interaction ◽  
Gene Environment

Abstract Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

Comparing Effects of FOXO3A and Residing in Urban Areas on Longevity: A Gene-Environment Interaction Study

2021 ◽  
Author(s):  
John S Ji ◽  
Linxin Liu ◽  
Lijing Yan ◽  
Yi Zeng
Keyword(s):  
Protective Effect ◽  
Effect Size ◽  
Urban Areas ◽  
Vegetation Index ◽  
Normalized Difference Vegetation Index ◽  
Fine Particulate Matter ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Gene Environment Interaction ◽  
Gene Environment

Abstract Forkhead box O3 (FOXO3A) is a candidate longevity gene. Urban residents are also positively associated with longer life expectancy. We conducted a gene-environment interaction to assess the synergistic effect of FOXO3A and urban/rural environments on mortality. We included 3085 older adults from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We used single nucleotide polymorphisms (SNPs) rs2253310, rs2802292, and rs4946936 to identify the FOXO3A gene and classified residential locations as "urban" and "rural." Given the open cohort design, we used the Cox-proportional hazard regression models to assess the mortality risk. We found the minor allele homozygotes of FOXO3A to have a protective effect on mortality [HR (95% CI) for rs4946936 TT vs. CC: 0.807 (0.653, 0.996); rs2802292 GG vs TT: 0.812 (0.67, 0.985); rs2253310 CC vs. GG: 0.808 (0.667, 0.978)]. Participants living in urban areas had a lower risk of mortality [HR of the urban vs. the rural: 0.854 (0.759, 0.962)]. The interaction between FOXO3A and urban and rural regions was statistically significant (pinteraction&lt;0.01). Higher air pollution (fine particulate matter: PM2.5) and lower residential greenness (Normalized Difference Vegetation Index: NDVI) both contributed to higher mortality. After adjusting for NDVI and PM2.5, the protective effect size of FOXO3A SNPs was slightly attenuated while the protective effect size of living in an urban environment increased. The effect size of the beneficial effect of FOXO3 on mortality is roughly equivalent to that of living in urban areas. Our research findings indicate the effect of places of residence and genetic predisposition of longevity are intertwined.

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