Long-term antibiotic use during early life and risks to mental traits: an observational study and gene–environment-wide interaction study in UK Biobank cohort

Abstract Objective To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults. Methods The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0. Results We observed positive association between SHBG and the frequency of alcohol consumption (b = 0.0101, p = 3.84 × 10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b = 0.0128, p = 1.96 × 10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = − 0.0136, p = 5.74 × 10–5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10–8) interacting with total testosterone for fluid intelligence. Conclusion Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.

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Transgenerational Transmission of Stress Pathology

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000219 ◽

2015 ◽

Vol 223 (3) ◽

pp. 181-191 ◽

Cited By ~ 2

Author(s):

Margarete Bolten

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Long Term Outcomes ◽

Gene Environment ◽

Stressful Experiences ◽

Rats And Mice ◽

The Impact ◽

Identical Gene

Abstract. The impact of the environment early in life on long-term outcomes is well known. Stressful experiences during pre- and postnatal development can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Furthermore, there is documented evidence for gene-environment interactions in the context of early-life stress. Identical gene variants can be associated with different phenotypes depending on environmental factors. DNA methylation, an enzymatically-catalyzed modification of the DNA, is the mechanism through which phenotypes are regulated. The dynamics and plasticity of epigenetic mechanisms can have short-term, long-term, or transgenerational consequences. In epigenetic research, rodent models have targeted several behavioral and emotional phenotypes. These models have contributed significantly to our understanding of the environmental regulation of the developmental brain in early life. This review will highlight studies with rats and mice on epigenetic processes in fetal programming of stress-related mental disorders.

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Interaction between antibiotic use and MS4A2 gene polymorphism on childhood eczema: a prospective birth cohort study

BMC Pediatrics ◽

10.1186/s12887-021-02786-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Li Hua ◽

Qian Chen ◽

Quan-Hua Liu ◽

Yi-Feng Guo ◽

Ru-Hong Cheng ◽

...

Keyword(s):

Birth Cohort ◽

Antibiotic Use ◽

Birth Cohort Study ◽

Chinese Han ◽

Replication Studies ◽

Gene Environment ◽

Long Term Follow Up ◽

History Of

Abstract Background Eczema is usually the first allergic manifestation to appear in life attributed to gene–environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children. Methods Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists. Results Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68). Conclusions MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.

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16 Long-term immune and metabolic consequences of a disrupted early life microbiota

Journal of Animal Science ◽

10.1093/jas/skz122.015 ◽

2019 ◽

Vol 97 (Supplement_2) ◽

pp. 9-9

Author(s):

Benjamin P Willing

Keyword(s):

Early Life ◽

Immune Cell ◽

Antibiotic Use ◽

Rapid Expansion ◽

Intestinal Lumen ◽

Immune Cell Population ◽

Subsequent Performance ◽

Long Term Impact ◽

And Function

Abstract In the first weeks of life, the gastrointestinal tract changes dramatically in structure and function, including a rapid expansion and maturation of the immune cell population. Successful intestinal development comes at a significant energy cost yet is essential to subsequent performance and health. Many of the developmental changes in intestinal and immune development are dependent on the abundant and diverse population of microbes (microbiota) residing at the mucosal surface and in the intestinal lumen. We are now beginning to understand that the nature of the first exposures in the first days to weeks of life have a long-term impact on physiological processes important to metabolic health, as well as immune programming that impacts response to pathogen challenge. In this presentation I will discuss our key findings on the significant impacts early life microbial disruption have on intestinal, pancreatic, and immune function of the piglet. I will also discuss the consequences of excessive hygiene on disease resilience as well as the ability to mount a successful immune response in response to vaccination. Understanding the ability of the early life microbiota to program subsequent health provides a significant opportunity to support healthy pig production as we move away from antibiotic use in livestock production.

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Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort

10.21203/rs.3.rs-32855/v4 ◽

2020 ◽

Author(s):

Xiao Liang ◽

ShiQiang Cheng ◽

Jing Ye ◽

XiaoMeng Chu ◽

Yan Wen ◽

...

Keyword(s):

Alcohol Consumption ◽

Fluid Intelligence ◽

Genetic Effects ◽

Sex Hormone ◽

Uk Biobank ◽

Interaction Study ◽

Middle Aged ◽

Bioavailable Testosterone ◽

Gene Environment ◽

Middle Aged Adults

Abstract Objective: To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.Methods: The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive association between SHBG and the frequency of alcohol consumption (b=0.0101, p=3.84×10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.0128, p=1,96×10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b=-0.0136, p=5.74×10-5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.

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Characterisation of insomnia as an environmental risk factor for asthma via Mendelian randomization and gene environment interaction

Scientific Reports ◽

10.1038/s41598-021-01291-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dong Jun Kim ◽

Tae-Woong Ha ◽

Hae Un Jung ◽

Eun Ju Baek ◽

Won Jun Lee ◽

...

Keyword(s):

Risk Factor ◽

Mendelian Randomization ◽

Meta Analysis ◽

Environment Interaction ◽

Summary Statistics ◽

Uk Biobank ◽

Interaction Study ◽

Gene Environment Interaction ◽

Gene Environment ◽

Causal Directionality

AbstractAsthma is a complex disease that is reportedly associated with insomnia. However, the causal directionality of this association is still unclear. We used asthma and insomnia-associated single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) summary statistics to test the causal directionality between insomnia and asthma via Mendelian randomization (MR) analysis. We also performed a cross-trait meta-analysis using UK Biobank GWAS summary statistics and a gene–environment interaction study using data from UK Biobank. The interaction of genetic risk score for asthma (GRSasthma) with insomnia on asthma was tested by logistic regression. Insomnia was a risk factor for the incidence of asthma, as revealed by three different methods of MR analysis. However, asthma did not act as a risk factor for insomnia. The cross-trait meta-analysis identified 28 genetic loci shared between asthma and insomnia. In the gene–environment interaction study, GRSasthma interacted with insomnia to significantly affect the risk of asthma. The results of this study highlight the importance of insomnia as a risk factor of asthma, and warrant further analysis of the mechanism through which insomnia affects the risk of asthma.

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