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

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.

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Interaction between ELMO1 gene polymorphisms and environment factors on susceptibility to diabetic nephropathy in Chinese Han population

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-019-0492-0 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Yi Hou ◽

Yong Gao ◽

Yan Zhang ◽

Si-Tong Lin ◽

Yue Yu ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Alcohol Drinking ◽

Control Group ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Gene Environment Interaction ◽

Gene Environment ◽

Increased Risk ◽

Significant Gene

Abstract Background The association of diabetic nephropathy (DN) risk with single nucleotide polymorphisms (SNPs) within Engulfment and Cell Motility 1 (ELMO1) gene and gene–environment synergistic effect have not been extensively examined in, therefore, the purpose of this study is to explore the association between multiple SNPs in ELMO1 gene, and the relationship between gene–environment synergy effect and the risk of DN. Methods Genotyping for 4 SNPs was performed with polymerase chain reaction (PCR) and following restriction fragment length polymorphism (RFLP) methods. Hardy–Weinberg balance of the control group was tested by SNPstats (online software: http://bioinfo.iconologia.net/snpstats). The best combination of four SNPs of ELMO1 gene and environmental factors was screened by GMDR model. Logistic regression was used to calculating the OR values between different genotypes of ELMO1 gene and DN. Results The rs741301-G allele and the rs10255208-GG genotype were associated with an increased risk of DN risk, adjusted ORs (95% CI) were 1.75 (1.19–2.28) and 1.41 (1.06–1.92), respectively, both p-values were < 0.001. We also found that the others SNPs-rs1345365 and rs7782979 were not significantly associated with susceptibility to DN. GMDR model found a significant gene–alcohol drinking interaction combination (p = 0.0107), but no significant gene–hypertension interaction combinations. Alcohol drinkers with rs741301-AG/GG genotype also have the highest DN risk, compared to never drinkers with rs741301-AA genotype, OR (95% CI) 3.52 (1.93–4.98). Conclusions The rs741301-G allele and the rs10255208-GG genotype, gene–environment interaction between rs741301 and alcohol drinking were all associated with increased DN risk.

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

BMC Cancer ◽

10.1186/s12885-021-08571-4 ◽

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.

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

The Journals of Gerontology Series A ◽

10.1093/gerona/glab362 ◽

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<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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Association of single‐nucleotide polymorphisms in TLR4 gene and gene–environment interaction with primary open angle glaucoma in a Chinese northern population

The Journal of Gene Medicine ◽

10.1002/jgm.3139 ◽

2019 ◽

Vol 22 (1) ◽

Author(s):

Huijuan Liu ◽

Shixin Qi ◽

Wei He ◽

Cuirong Chang ◽

Yanhui Chen ◽

...

Keyword(s):

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Open Angle ◽

Northern Population ◽

Single Nucleotide ◽

Gene Environment Interaction ◽

Gene Environment ◽

Tlr4 Gene

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5,10-Methylenetetrahydrofolate reductase single nucleotide polymorphisms and gene-environment interaction analysis in non-syndromic cleft lip/palate

European Journal Of Oral Sciences ◽

10.1111/eos.12114 ◽

2014 ◽

Vol 122 (2) ◽

pp. 109-113 ◽

Cited By ~ 16

Author(s):

Bernardette Estandia-Ortega ◽

José A. Velázquez-Aragón ◽

Miguel A. Alcántara-Ortigoza ◽

Miriam E. Reyna-Fabian ◽

Sandra Villagómez-Martínez ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Cleft Lip ◽

Methylenetetrahydrofolate Reductase ◽

Interaction Analysis ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Gene Environment Interaction ◽

Gene Environment ◽

Cleft Lip Palate

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Early-onset Alzheimer's disease in Scotland: environmental and familial factors

The British Journal of Psychiatry ◽

10.1192/bjp.178.40.s53 ◽

2001 ◽

Vol 178 (S40) ◽

pp. s53-s59 ◽

Cited By ~ 17

Author(s):

Lawrence J. Whalley

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Environmental Factors ◽

Disease Model ◽

Environmental Data ◽

Paternal Age ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment ◽

Genetic And Environmental Factors

BackgroundAlzheimer's disease (AD) is a common, complex, age-related disorder in which both genetic and environmental factors are important.AimsTo integrate recent studies on genetic and environmental factors in AD into a multi-factorial disease model.MethodDisease models to explain gene-environment interaction in cardiovascular disease are related to observations on AD.ResultsInformative, community-based studies on the genetic epidemiology of AD are rare. Putative risk factors from the Scottish studies include increased paternal age in AD men and coal mining as paternal occupation in both AD and vascular dementia. Migration effects suggest that environmental factors in high-incidence AD areas are important during adult life.ConclusionsThe studies summarised do not provide sufficient data to support a single comprehensive disease model of gene-environment interaction in AD. Future studies will require very large (≥600) sample sizes, molecular genetic analysis, and environmental data that span neurodevelopment and the period between disease onset and appearance of clinical symptoms.

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The Role of Gene–Environment Interaction in Determining Bone Mineral Density in a Twin Population

Twin Research and Human Genetics ◽

10.1375/twin.10.1.191 ◽

2007 ◽

Vol 10 (1) ◽

pp. 191-197 ◽

Cited By ~ 1

Author(s):

Vasi Naganathan ◽

Alexander J. MacGregor ◽

Philip N. Sambrook

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Environmental Factors ◽

Bone Mineral ◽

Genetic Component ◽

Total Variance ◽

Environment Interaction ◽

Mineral Density ◽

Gene Environment Interaction ◽

Gene Environment

AbstractThe possibility that specific environmental factors such as smoking and estrogen use modify the genetic influences (gene–environment interaction) on bone mineral density (BMD) has not been explored in genetic epidemiological studies such as twin studies. The aim of this study was to look for evidence of gene–environment interaction in BMD determination by analyzing data collected on a large number of healthy female twins. BMD of the hip, distal forearm and lumbar spine were measured by dual-energy X-ray absorptiometry on 287 identical and 265 nonidentical volunteer female twin pairs. The environmental factors examined were hormone replacement therapy (HRT) and smoking. In genetic modeling analysis using path analysis, there was evidence of ‘HRT-specific’ genetic component of BMD variance at the forearm (50% of total variance) but not at the hip. At the lumbar spine the magnitude of the genetic component of variance in HRT users (> 60-month HRT use) was less than the genetic component of variance for little or no exposure to HRT (48% vs. 84%). There was no evidence of gene–environment interaction for smoking. The main evidence for gene–environment interaction was the finding that forearm BMD variance was influenced by a significant HRT-specific genetic component. There was also evidence that in HRT users, the genetic component of total variance for lumbar BMD was lower.

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Effects of Gene-Environment Interaction on Obesity among Chinese Adults Born in the Early 1960s

Genes ◽

10.3390/genes12020270 ◽

2021 ◽

Vol 12 (2) ◽

pp. 270

Author(s):

Weiyan Gong ◽

Hui Li ◽

Chao Song ◽

Fan Yuan ◽

Yanning Ma ◽

...

Keyword(s):

Socioeconomic Status ◽

Waist Circumference ◽

Environmental Factors ◽

Central Obesity ◽

Environment Interaction ◽

Sedentary Behaviors ◽

Chinese Adults ◽

Gene Environment Interaction ◽

Gene Environment ◽

Fto Rs9939609

The prevalence of obesity has been increasing sharply and has become a serious public health problem worldwide. Gene–environment interaction in obesity is a relatively new field, and little is known about it in Chinese adults. This study aimed to provide the effects of gene–environment interaction on obesity among Chinese adults. A stratified multistage cluster sampling method was conducted to recruit participants from 150 surveillance sites. Subjects born in 1960, 1961 and 1963 were selected. An exploratory factor analysis was used to classify the environmental factors. The interaction of single nucleotide polymorphisms (SNPs) and environmental factors on body mass index (BMI) and waist circumference were analyzed using a general linear model. A multiple logistic regression model combined with an additive model was performed to analyze the interaction between SNPs and environmental factors in obesity and central obesity. A total of 2216 subjects were included in the study (mean age, 49.7 years; male, 39.7%, female, 60.3%). Engaging in physical activity (PA) could reduce the effect of MC4R rs12970134 on BMI (β = −0.16kg/m2, p = 0.030), and also reduce the effect of TRHR rs7832552 and BCL2 rs12454712 on waist circumference (WC). Sedentary behaviors increased the effects of SNPs on BMI and WC, and simultaneously increased the effects of FTO rs9939609 and FTO rs8050136 on obesity and central obesity. A higher socioeconomic status aggravated the influence of SNPs (including FTO rs9939609, BNDF rs11030104, etc.) on BMI and WC, and aggravated the influence of SEC16B rs574367 on central obesity. The MC4R rs12970134 association with BMI and the FTO rs8050136 association with central obesity appeared to be more pronounced with higher energy intake (β = 0.140 kg/m2, p = 0.049; OR = 1.77, p = 0.004, respectively). Engaging in PA could reduce the effects of SNPs on BMI and WC; nevertheless, a higher socioeconomic status, higher dietary energy intake and sedentary behaviors accentuated the influences of SNPs on BMI, WC, obesity and central obesity. Preventative measures for obesity should consider addressing the gene–environment interaction.

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Gene–environment interaction

Practical Psychiatric Epidemiology ◽

10.1093/med/9780198735564.003.0020 ◽

2020 ◽

pp. 343-358

Author(s):

Craig Morgan ◽

Marta Di Forti ◽

Helen L. Fisher

Keyword(s):

Mental Disorders ◽

Environmental Factors ◽

Statistical Modelling ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Working Definition ◽

Gene Environment ◽

Genetic And Environmental Factors ◽

Definition Of ◽

Study Designs

For all major mental disorders there are many factors that, in combination and through multiple pathways, increase or decrease the risk of onset. These include, to varying degrees, genetic and environmental factors. This chapter provides an introduction, from an epidemiological perspective, to the study of gene–environment interaction. It begins by providing a working definition of gene–environment interaction, rooted in a sufficient causes framework, and then considers, in turn, the prominent puzzles and challenges, including the statistical modelling of interaction, the main study designs (including strengths and weaknesses), measurement of environmental exposures, and required sample sizes. The chapter concludes with a consideration of the implications of recent advances in genetics for studies of gene–environment interaction.

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