scholarly journals Genome-wide stress sensitivity moderates the stress-depression relationship in a nationally representative sample of adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Trent Davidson ◽  
David B. Braudt ◽  
Robert Keers ◽  
Elham Assary ◽  
Kathleen Mullan Harris ◽  
...  
Keyword(s):  
Add Health ◽  
Stress Sensitivity ◽  
Environment Interaction ◽  
Genetic Determinants ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
Nationally Representative ◽  
The Relationship

AbstractWe re-evaluate the findings of one of the most cited and disputed papers in gene-environment interaction (GxE) literature. In 2003, a paper was published in Science in which the authors demonstrated that the relationship between stress and depression is moderated by a polymorphism in the promoter region (5-HTTLPR) of the gene SLC6A4. Replication has been weak and led many to challenge the overall significance of GxE research. Here, we utilize data from Add Health, a large, nationally representative, and well-powered longitudinal study to re-examine the genetic determinants of stress sensitivity. We characterize environmental sensitivity using a genome-wide polygenic indicator rather than relying on one polymorphism in a single candidate gene. Our results provide support for the stress-diathesis perspective and validate the scientific contributions of the original paper.

scholarly journals Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate

2011 ◽  
pp. n/a-n/a ◽  
Author(s):  
Terri H. Beaty ◽  
Ingo Ruczinski ◽  
Jeffrey C. Murray ◽  
Mary L. Marazita ◽  
Ronald G. Munger ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Study

scholarly journals Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes

2017 ◽  
Vol 29 (1) ◽  
pp. 335-348 ◽  
Author(s):  
Tanguy Corre ◽  
Francisco J. Arjona ◽  
Caroline Hayward ◽  
Sonia Youhanna ◽  
Jeroen H.F. de Baaij ◽  
...  
Keyword(s):  
General Population ◽  
Meta Analysis ◽  
Human Kidney ◽  
Environment Interaction ◽  
Genetic Determinants ◽  
Metabolic Disturbances ◽  
Renal Handling ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome

Magnesium (Mg2+) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10−13) near TRPM6, which encodes an epithelial Mg2+ channel, and rs35929 (P=2.1×10−11), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg2+ regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene–environment interaction linking Mg2+ deficiency to insulin resistance and obesity.

scholarly journals CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children’s Oncology Group Genome-Wide Association Study

2016 ◽  
Vol 34 (8) ◽  
pp. 863-870 ◽  
Author(s):  
Xuexia Wang ◽  
Can-Lan Sun ◽  
Adolfo Quiñones-Lombraña ◽  
Purnima Singh ◽  
Wendy Landier ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Dose Dependent

Purpose Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests that genetic susceptibility could play a role. The current study uses an agnostic approach to identify genetic variants that could modify cardiomyopathy risk. Methods A genome-wide association study was conducted in childhood cancer survivors with and without cardiomyopathy (cases and controls, respectively). Single-nucleotide polymorphisms (SNPs) that surpassed a prespecified threshold for statistical significance were independently replicated. The possible mechanistic significance of validated SNP(s) was sought by using healthy heart samples. Results No SNP was marginally associated with cardiomyopathy. However, SNP rs1786814 on the CELF4 gene passed the significance cutoff for gene-environment interaction (Pge = 1.14 × 10−5). Multivariable analyses adjusted for age at cancer diagnosis, sex, anthracycline dose, and chest radiation revealed that, among patients with the A allele, cardiomyopathy was infrequent and not dose related. However, among those exposed to greater than 300 mg/m2 of anthracyclines, the rs1786814 GG genotype conferred a 10.2-fold (95% CI, 3.8- to 27.3-fold; P < .001) increased risk of cardiomyopathy compared with those who had GA/AA genotypes and anthracycline exposure of 300 mg/m2 or less. This gene-environment interaction was successfully replicated in an independent set of anthracycline-related cardiomyopathy. CUG-BP and ETR-3-like factor proteins control developmentally regulated splicing of TNNT2, the gene that encodes for cardiac troponin T (cTnT), a biomarker of myocardial injury. Coexistence of more than one cTnT variant results in a temporally split myofilament response to calcium, which causes decreased contractility. Analysis of TNNT2 splicing variants in healthy human hearts suggested an association between the rs1786814 GG genotype and coexistence of more than one TNNT2 splicing variant (90.5% GG v 41.7% GA/AA; P = .005). Conclusion We report a modifying effect of a polymorphism of CELF4 (rs1786814) on the dose-dependent association between anthracyclines and cardiomyopathy, which possibly occurs through a pathway that involves the expression of abnormally spliced TNNT2 variants.

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