scholarly journals Multi-omics insights into the biological mechanisms underlying gene-by-lifestyle interactions with smoking and alcohol consumption detected by genome-wide trans-ancestry meta-analysis

2021 ◽  
Author(s):  
Timothy D Majarian ◽  
Amy R Bentley ◽  
Vincent Laville ◽  
Michael R Brown ◽  
Daniel I Chasman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Alcohol Consumption ◽  
Genetic Variants ◽  
Blood Lipids ◽  
Epigenetic Modification ◽  
Smoking Behavior ◽  
Lifestyle Factors ◽  
Biological Mechanisms ◽  
Genome Wide

Gene-lifestyle interaction analyses have identified genetic variants whose effect on cardiovascular risk-raising traits is modified by alcohol consumption and smoking behavior. The biological mechanisms of these interactions remain largely unknown, but may involve epigenetic modification linked to perturbation of gene expression. Diverse, individual-level datasets including genotypes, methylation and gene expression conditional on lifestyle factors, are ideally suited to study this hypothesis, yet are often unavailable for large numbers of individuals. Summary-level data, such as effect sizes of genetic variants on a phenotype, present an opportunity for multi-omic study of the biological mechanisms underlying gene-lifestyle interactions. We propose a method that unifies disparate, publicly available summary datasets to build mechanistic hypotheses in models of smoking behavior and alcohol consumption with blood lipid levels and blood pressure measures. Of 897 observed genetic interactions, discovered through genome-wide analysis in diverse multi-ethnic cohorts, 48 were identified with lifestyle-related differentially methylated sites within close proximity and linked to target genes. Smoking behavior and blood lipids account for 37 and 28 of these signals respectively. Five genes also showed differential expression conditional on lifestyle factors within these loci with mechanisms supported in the literature. Our analysis demonstrates the utility of summary data in characterizing observed gene-lifestyle interactions and prioritizes genetic loci for experimental follow up related to blood lipids, blood pressure, and cigarette smoking. We show concordance between multiple trait- or exposure-related associations from diverse assays, driving hypothesis generation for better understanding gene-lifestyle interactions.

scholarly journals Modifiable lifestyle factors and severe COVID-19 risk: a Mendelian randomisation study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shuai Li ◽  
Xinyang Hua
Keyword(s):  
Physical Activity ◽  
Alcohol Consumption ◽  
Genetic Variants ◽  
Association Studies ◽  
Lifestyle Factors ◽  
Mendelian Randomisation ◽  
Severe Illness ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Increased Risk

Abstract Background Lifestyle factors including obesity and smoking are suggested to be correlated with increased risk of COVID-19 severe illness or related death. However, whether these relationships are causal is not well known; neither for the relationships between COVID-19 severe illness and other common lifestyle factors, such as physical activity and alcohol consumption. Methods Genome-wide significant genetic variants associated with body mass index (BMI), lifetime smoking, physical activity and alcohol consumption identified by large-scale genome-wide association studies (GWAS) of up to 941,280 individuals were selected as instrumental variables. Summary statistics of the genetic variants on severe illness of COVID-19 were obtained from GWAS analyses of up to 6492 cases and 1,012,809 controls. Two-sample Mendelian randomisation analyses were conducted. Results Both per-standard deviation (SD) increase in genetically predicted BMI and lifetime smoking were associated with about two-fold increased risks of severe respiratory COVID-19 and COVID-19 hospitalization (all P < 0.05). Per-SD increase in genetically predicted physical activity was associated with decreased risks of severe respiratory COVID-19 (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.05, 0.74; P = 0.02), but not with COVID-19 hospitalization (OR = 0.44; 95% CI 0.18, 1.07; P = 0.07). No evidence of association was found for genetically predicted alcohol consumption. Similar results were found across robust Mendelian randomisation methods. Conclusions Evidence is found that BMI and smoking causally increase and physical activity might causally decrease the risk of COVID-19 severe illness. This study highlights the importance of maintaining a healthy lifestyle in protecting from COVID-19 severe illness and its public health value in fighting against COVID-19 pandemic.

scholarly journals Modifiable lifestyle factors and severe COVID-19 risk: Evidence from Mendelian randomization analysis

2020 ◽  
Author(s):  
Shuai Li
Keyword(s):  
Physical Activity ◽  
Alcohol Consumption ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Lifestyle Factors ◽  
Severe Illness ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Increased Risk

AbstractBackgroundLifestyle factors including obesity and smoking are suggested to be related to increased risk of COVID-19 severe illness or related death. However, little is known about whether these relationships are causal, or the relationships between COVID-19 severe illness and other lifestyle factors, such as alcohol consumption and physical activity.MethodsGenome-wide significant genetic variants associated with body mass index (BMI), lifetime smoking, alcohol consumption and physical activity identified by large-scale genome-wide association studies (GWAS) were selected as instrumental variables. GWAS summary statistics of these genetic variants for relevant lifestyle factors and severe illness of COVID-19 were obtained. Two-sample Mendelian randomization (MR) analyses were conducted.ResultsBoth genetically predicted BMI and lifetime smoking were associated with about 2-fold increased risks of severe respiratory COVID-19 and COVID-19 hospitalization (all P<0.05). Genetically predicted physical activity was associated with about 5-fold (95% confidence interval [CI], 1.4, 20.3; P=0.02) decreased risk of severe respiratory COVID-19, but not with COVID-19 hospitalization, though the majority of the 95% CI did not include one. No evidence of association was found for genetically predicted alcohol consumption, but associations were found when using pleiotropy robust methods.ConclusionEvidence is found that BMI and smoking causally increase and physical activity causally decreases the risk of COVID-19 severe illness. This study highlights the importance of maintaining a healthy lifestyle in protecting from COVID-19 severe illness and its public health value in fighting against COVID-19 pandemic.

scholarly journals Genome-wide H3K9 Acetylation Level Increases with Age-Dependent Senescence of Flag Leaf in Rice (Oryza sativa)

2021 ◽  
Author(s):  
Yu Zhang ◽  
Yanyun Li ◽  
Yuanyuan Zhang ◽  
Zeyu Zhang ◽  
Deyu Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oryza Sativa ◽  
Leaf Senescence ◽  
Epigenetic Modification ◽  
Flag Leaf ◽  
Regulation Of Gene Expression ◽  
Leaf Aging ◽  
Genome Wide ◽  
Age Dependent ◽  
H3k9 Acetylation

Flag leaf senescence is an important biological process that drives the remobilization of nutrients to the growing organs of rice. Leaf senescence is controlled by genetic information via gene expression and epigenetic modification, but the precise mechanism is as of yet unclear. Here, we analyzed genome-wide acetylated lysine residue 9 of histone H3 (H3K9ac) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq) and examined its association with transcriptomes by RNA-seq during flag leaf aging in rice (Oryza sativa). We found that genome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and there was a positive correlation between the density and breadth of H3K9ac and gene expression and transcript elongation. A set of 1,249 up-regulated, differentially expressed genes (DEGs) and 996 down-regulated DEGs showing a strong relationship between temporal changes in gene expression and gain/loss of H3K9ac was observed during rice flag leaf aging. We produced a landscape of H3K9 acetylation- modified gene expression targets that includes known senescence-associated genes, metabolism-related genes, as well as miRNA biosynthesis- related genes. Our findings reveal a complex regulatory network of metabolism- and senescence-related pathways mediated by H3K9ac and also elucidate patterns of H3K9ac-mediated regulation of gene expression during flag leaf aging in rice.

scholarly journals A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome

2019 ◽  
Author(s):  
Tom G Richardson ◽  
Gibran Hemani ◽  
Tom R Gaunt ◽  
Caroline L Relton ◽  
George Davey Smith
Keyword(s):  
Gene Expression ◽  
Genetic Variants ◽  
Complex Traits ◽  
Mendelian Randomization ◽  
Drug Repositioning ◽  
Association Studies ◽  
Thyroid Tissue ◽  
Genome Wide Association Studies ◽  
Tissue Specific ◽  
Genome Wide

AbstractBackgroundDeveloping insight into tissue-specific transcriptional mechanisms can help improve our understanding of how genetic variants exert their effects on complex traits and disease. By applying the principles of Mendelian randomization, we have undertaken a systematic analysis to evaluate transcriptome-wide associations between gene expression across 48 different tissue types and 395 complex traits.ResultsOverall, we identified 100,025 gene-trait associations based on conventional genome-wide corrections (P < 5 × 10−08) that also provided evidence of genetic colocalization. These results indicated that genetic variants which influence gene expression levels in multiple tissues are more likely to influence multiple complex traits. We identified many examples of tissue-specific effects, such as genetically-predicted TPO, NR3C2 and SPATA13 expression only associating with thyroid disease in thyroid tissue. Additionally, FBN2 expression was associated with both cardiovascular and lung function traits, but only when analysed in heart and lung tissue respectively.We also demonstrate that conducting phenome-wide evaluations of our results can help flag adverse on-target side effects for therapeutic intervention, as well as propose drug repositioning opportunities. Moreover, we find that exploring the tissue-dependency of associations identified by genome-wide association studies (GWAS) can help elucidate the causal genes and tissues responsible for effects, as well as uncover putative novel associations.ConclusionsThe atlas of tissue-dependent associations we have constructed should prove extremely valuable to future studies investigating the genetic determinants of complex disease. The follow-up analyses we have performed in this study are merely a guide for future research. Conducting similar evaluations can be undertaken systematically at http://mrcieu.mrsoftware.org/Tissue_MR_atlas/.

Lifestyle factors and genetic variants on two biological age measures: evidence from 94,443 Taiwan Biobank participants

2021 ◽  
Author(s):  
Wan-Yu Lin
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Lifestyle Factors ◽  
Biological Age ◽  
Biological Aging ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
The Uk

Abstract Background Biological age (BA) can be estimated by phenotypes and is useful for predicting lifespan and healthspan. Levine et al. proposed a PhenoAge and a BioAge to measure BA. Although there have been studies investigating the genetic predisposition to BA acceleration in Europeans, little has been known regarding this topic in Asians. Methods I here estimated PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 94,443 Taiwan Biobank (TWB) participants, wherein 25,460 TWB1 subjects formed a discovery cohort and 68,983 TWB2 individuals constructed a replication cohort. Lifestyle factors and genetic variants associated with PhenoAgeAccel and BioAgeAccel were investigated through regression analysis and a genome-wide association study (GWAS). Results A unit (kg/m 2) increase of BMI was associated with a 0.177-year PhenoAgeAccel (95% C.I. = 0.163~0.191, p = 6.0×) and 0.171-year BioAgeAccel (95% C.I. = 0.165~0.177, p = 0). Smokers on average had a 1.134-year PhenoAgeAccel (95% C.I. = 0.966~1.303, p = 1.3×) compared with non-smokers. Drinkers on average had a 0.640-year PhenoAgeAccel (95% C.I. = 0.433~0.847, p = 1.3×) and 0.193-year BioAgeAccel (95% C.I. = 0.107~0.279, p = 1.1×) relative to non-drinkers. A total of 11 and 4 single-nucleotide polymorphisms (SNPs) were associated with PhenoAgeAccel and BioAgeAccel (p&lt;5× in both TWB1 and TWB2), respectively. Conclusions A PhenoAgeAccel-associated SNP (rs1260326 in GCKR) and two BioAgeAccel-associated SNPs (rs7412 in APOE; rs16998073 near FGF5) were consistent with the finding from the UK Biobank. The lifestyle analysis shows that prevention from obesity, cigarette smoking, and alcohol consumption is associated with a slower rate of biological aging.

scholarly journals Genome-Wide DNA Methylation Profiling in the Lotus (Nelumbo nucifera) Flower Showing its Contribution to the Stamen Petaloid

Plants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 135 ◽  
Author(s):  
Zhongyuan Lin ◽  
Meihui Liu ◽  
Rebecca Njeri Damaris ◽  
Tonny Maraga Nyong’a ◽  
Dingding Cao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Epigenetic Modification ◽  
Nelumbo Nucifera ◽  
Flower Formation ◽  
Relationship Analysis ◽  
Genome Wide ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

DNA methylation is a vital epigenetic modification. Methylation has a significant effect on the gene expression influencing the regulation of different physiological processes. Current studies on DNA methylation have been conducted on model plants. Lotus (Nelumbo nucifera) is a basic eudicot exhibiting variations during development, especially in flower formation. DNA methylation profiling was conducted on different flower tissues of lotuses through whole genome bisulfite sequencing (WGBS) to investigate the effects of DNA methylation on its stamen petaloid. A map of methylated cytosines at the single base pair resolution for the lotus was constructed. When the stamen was compared with the stamen petaloid, the DNA methylation exhibited a global decrease. Genome-wide relationship analysis between DNA methylation and gene expression identified 31 different methylation region (DMR)-associated genes, which might play crucial roles in floral organ formation, especially in the stamen petaloid. One out of 31 DMR-associated genes, NNU_05638 was homolog with Plant U-box 33 (PUB33). The DNA methylation status of NNU_05638 promoter was distinct in three floral organs, which was confirmed by traditional bisulfite sequencing. These results provide further insights about the regulation of stamen petaloids at the epigenetic level in lotus.

Abstract 2195: Genome-wide interaction analyses between genetic variants and alcohol consumption and risk of colorectal cancer

2014 ◽  
Author(s):  
Jian Gong ◽  
Carolyn Hutter ◽  
Jenny Chang-Claude ◽  
Polly Newcomb ◽  
Sonja Berndt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Alcohol Consumption ◽  
Genetic Variants ◽  
Genome Wide

scholarly journals A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits

PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0157776 ◽  
Author(s):  
Petr Volkov ◽  
Anders H. Olsson ◽  
Linn Gillberg ◽  
Sine W. Jørgensen ◽  
Charlotte Brøns ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Genetic Variants ◽  
Human Adipose Tissue ◽  
Metabolic Traits ◽  
Genome Wide ◽  
A Genome

scholarly journals Gene-based association analysis identified 190 genes with polymorphisms affecting neuroticism

2020 ◽  
Author(s):  
Nadezhda M. Belonogova ◽  
Irina V. Zorkoltseva ◽  
Yakov A. Tsepilov ◽  
Tatiana I. Axenovich
Keyword(s):  
Gene Expression ◽  
Detailed Analysis ◽  
Association Analysis ◽  
Genetic Variants ◽  
Bioinformatics Analysis ◽  
Summary Statistics ◽  
Uk Biobank ◽  
Protein Coding ◽  
Pathogenic Variants ◽  
Genome Wide

AbstractRecent genome-wide studies have reported about 600 genes potentially influencing neuroticism. Little is known about the mechanisms of their action. Here, we aimed to conduct a more detailed analysis of genes whose polymorphisms can regulate the level of neuroticism. Using UK Biobank-based GWAS summary statistics, we performed a gene-based association analysis using four sets of genetic variants within a gene differing in their protein coding properties. To guard against the influence of strong GWAS signals outside the gene, we used the specially designed procedure. As a result, we identified 190 genes associated with neuroticism due to their polymorphisms. Thirty eight of these genes were novel. Within all genes identified, we distinguished two slightly overlapping groups comprising genes that demonstrated association when using protein-coding and non-coding SNPs. Many genes from the first group included potentially pathogenic variants. For some genes from the second group, we found evidence of pleiotropy with gene expression. We demonstrated that the association of almost two hundred known genes could be inflated by the GWAS signals outside the gene. Using bioinformatics analysis, we prioritized the neuroticism genes and showed that the genes influencing the trait by their polymorphisms are the most appropriate candidate genes.

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