TwinssCan — Gene-Environment Interaction in Psychotic and Depressive Intermediate Phenotypes: Risk and Protective Factors in a General Population Twin Sample

2019 ◽  
Vol 22 (6) ◽  
pp. 460-466 ◽  
Author(s):  
Lotta-Katrin Pries ◽  
Clara Snijders ◽  
Claudia Menne-Lothmann ◽  
Jeroen Decoster ◽  
Ruud van Winkel ◽  
...  
Keyword(s):  
General Population ◽  
Social Defeat ◽  
Reward Sensitivity ◽  
Environment Interaction ◽  
Affective Dysregulation ◽  
Intermediate Phenotypes ◽  
Gene Environment ◽  
National Networks ◽  
Meta Analyses ◽  
Adult Twins

AbstractMeta-analyses suggest that clinical psychopathology is preceded by dimensional behavioral and cognitive phenotypes such as psychotic experiences, executive functioning, working memory and affective dysregulation that are determined by the interplay between genetic and nongenetic factors contributing to the severity of psychopathology. The liability to mental ill health can be psychometrically measured using experimental paradigms that assess neurocognitive processes such as salience attribution, sensitivity to social defeat and reward sensitivity. Here, we describe the TwinssCan, a longitudinal general population twin cohort, which comprises 1202 individuals (796 adolescent/young adult twins, 43 siblings and 363 parents) at baseline. The TwinssCan is part of the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia project and recruited from the East Flanders Prospective Twin Survey. The main objective of this project is to understand psychopathology by evaluating the contribution of genetic and nongenetic factors on subclinical expressions of dimensional phenotypes at a young age before the onset of disorder and their association with neurocognitive processes, such as salience attribution, sensitivity to social defeat and reward sensitivity.

scholarly journals Neighborhood deprivation and depression in adult twins: genetics and gene×environment interaction

2016 ◽  
Vol 47 (4) ◽  
pp. 627-638 ◽  
Author(s):  
E. Strachan ◽  
G. Duncan ◽  
E. Horn ◽  
E. Turkheimer
Keyword(s):  
Additive Genetic Variance ◽  
Monozygotic Twin ◽  
Policy Implications ◽  
Environment Interaction ◽  
Environmental Variance ◽  
Neighborhood Deprivation ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Underlying Causes ◽  
Adult Twins

BackgroundDepression is a significant problem and it is vital to understand its underlying causes and related policy implications. Neighborhood characteristics are implicated in depression but the nature of this association is unclear. Unobserved or unmeasured factors may confound the relationship. This study addresses confounding in a twin study investigating neighborhood-level effects on depression controlling for genetics, common environment, and gene×environment (G × E) interactions.MethodData on neighborhood deprivation and depression were gathered from 3155 monozygotic twin pairs and 1275 dizygotic pairs (65.7% female) between 2006 and 2013. The variance for both depression and neighborhood deprivation was decomposed into three components: additive genetic variance (A); shared environmental variance (C); and non-shared environmental variance (E). Depression was then regressed on neighborhood deprivation to test the direct association and whether that association was confounded. We also tested for a G × E interaction in which the heritability of depression was modified by the level of neighborhood deprivation.ResultsDepression and neighborhood deprivation showed evidence of significant A (21.8% and 15.9%, respectively) and C (13.9% and 32.7%, respectively) variance. Depression increased with increasing neighborhood deprivation across all twins (p = 0.009), but this regression was not significant after controlling for A and C variance common to both phenotypes (p = 0.615). The G × E model showed genetic influences on depression increasing with increasing neighborhood deprivation (p < 0.001).ConclusionsNeighborhood deprivation is an important contributor to depression via increasing the genetic risk. Modifiable pathways that link neighborhoods to depression have been proposed and should serve as targets for intervention and research.

Urine cadmium levels and albuminuria in a general population from Spain: A gene-environment interaction analysis

2017 ◽  
Vol 106 ◽  
pp. 27-36 ◽  
Author(s):  
Maria Grau-Perez ◽  
Gernot Pichler ◽  
Inma Galan-Chilet ◽  
Laisa S. Briongos-Figuero ◽  
Pilar Rentero-Garrido ◽  
...  
Keyword(s):  
General Population ◽  
Interaction Analysis ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Urine Cadmium

The BDNF-Val66Met polymorphism modulates parental rearing effects on adult psychiatric symptoms: A community twin-based study

2014 ◽  
Vol 29 (5) ◽  
pp. 293-300 ◽  
Author(s):  
P. Ibarra ◽  
S. Alemany ◽  
M. Fatjó-Vilas ◽  
A. Córdova-Palomera ◽  
X. Goldberg ◽  
...  
Keyword(s):  
Maternal Care ◽  
Paternal Care ◽  
Psychiatric Symptoms ◽  
Brief Symptom Inventory ◽  
Environment Interaction ◽  
Paranoid Ideation ◽  
Val66met Polymorphism ◽  
Gene Environment ◽  
Parental Rearing ◽  
Adult Twins

AbstractPurpose:To test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding.Method:Perceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population.Results:In the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization.Conclusions:Met carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding.

Abstract MP067: Six Novel Loci With Evidence For Sexual Dimorphism For Human Anthropometric Traits From Genome-wide Meta Analyses Across 270,722 Individuals

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
J C Randall ◽  
T W Winkler ◽  
Z Kutalik ◽  
S I Berndt ◽  
A U Jackson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Sexual Dimorphism ◽  
Sex Difference ◽  
Environment Interaction ◽  
Sexually Dimorphic ◽  
P Values ◽  
Gene Environment ◽  
Genome Wide ◽  
Meta Analyses

Height, adiposity, and fat distribution differ in men and women and, in part, may explain sex differences in susceptibilities to complex diseases like cardiovascular disease. Genome-wide association studies (GWAS) of these traits have previously reported sexually dimorphic associations, yet studies have primarily been limited to interrogation of variants with genome wide significant main effects only. Because of these biological differences by sex and as there is growing interest in the study of gene-environment interactions in the context of GWAS in general, we conducted sex-specific meta-analyses of 9 phenotypes: height (HT), weight (WT), body mass index (BMI), waist circumference (WC), hip circumference (HIP), WC/HC ratio (WHR), WC adjusted for BMI (WCadjBMI), HC adjusted for BMI (HCadjBMI), and WHR adjusted for BMI (WHRadjBMI). In the discovery stage, we performed sex-specific meta-analyses of 46 GWAS, comprising 60,586 men and 73,137 women. Each study used an additive model to test up to ∼2.8M imputed SNPs for association with inverse-normal transformed phenotypes. From our first scan based on the sex-specific association P-values (P women , P men ) across all phenotypes, we selected 619 independent SNPs at a false discovery rate (FDR) of 5% to take forward to replication. We also conducted a second scan based on the P-value for sex difference (P sex-diff ) with better power to detect signals of opposite effect direction, yet we did not detect any signal at FDR of 5%. Follow-up of the 619 SNPs in up to 62,395 men and 74,657 women, many of which were genotyped on Metabochip, a custom Illumina iSelect array to which we submitted sex-specific SNPs, resulted in 205 loci with genome-wide significanct (P women or P men < 5x10 -8 ) p values in the combined discovery and follow-up analysis. For those 205 loci, we found 4 loci with significant (P sex-diff < 0.05/205) and 14 loci with suggestive (P sex-diff <0.05) evidence for sex-difference including known sexually dimorphic associations with anthropometric traits ( GRB14 , 1q41 , VEGFA , ADAMTS9), known anthropometric trait associations without any prior evidence for sexual-dimorphism ( 14q23.1, 3q21.3, 6q14.1, 4q12, 12q24.31, SEC16B, 17q21.32 , and 13q31.3 ), and novel sex-specific associations with anthropometric traits ( 5q11.2, 5q23.1, PPARG, 2q37.1, 17p11.2 , and 5q35.1 ). Interestingly, we found that our replicated loci for WHR/WC were enriched with markers with sex-differences, and that these genetic effects were uniformly stronger in women compared to men. Collectively, these results underscore the gain from sex-stratified GWAS in order to better pinpoint the genetics of complex traits and illustrate a sexually dimorphic genetic underpinning to some of these traits. Our results more globally emphasize the need to consider gene-environment interaction when searching for genes influencing risk to complex disease.

“Reports of My Death Were Greatly Exaggerated”: Behavior Genetics in the Postgenomic Era

2021 ◽  
Vol 72 (1) ◽  
pp. 37-60 ◽  
Author(s):  
K. Paige Harden
Keyword(s):  
Large Scale ◽  
Behavior Genetics ◽  
Behavioral Genetics ◽  
Association Studies ◽  
Environment Interaction ◽  
Genome Wide Association Studies ◽  
New Methods ◽  
Gene Environment ◽  
Meta Analyses ◽  
And Behavior

Behavior genetics studies how genetic differences among people contribute to differences in their psychology and behavior. Here, I describe how the conclusions and methods of behavior genetics have evolved in the postgenomic era in which the human genome can be directly measured. First, I revisit the first law of behavioral genetics stating that everything is heritable, and I describe results from large-scale meta-analyses of twin data and new methods for estimating heritability using measured DNA. Second, I describe new methods in statistical genetics, including genome-wide association studies and polygenic score analyses. Third, I describe the next generation of work on gene × environment interaction, with a particular focus on how genetic influences vary across sociopolitical contexts and exogenous environments. Genomic technology has ushered in a golden age of new tools to address enduring questions about how genes and environments combine to create unique human lives.

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 Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study

2019 ◽  
Vol 50 (11) ◽  
pp. 1884-1897 ◽  
Author(s):  
Jim van Os ◽  
Lotta-Katrin Pries ◽  
Philippe Delespaul ◽  
Gunter Kenis ◽  
Jurjen J. Luykx ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Psychotic Disorder ◽  
Genetic Risk ◽  
Environment Interaction ◽  
Replication Sample ◽  
Polygenic Risk ◽  
Gene Environment Interaction ◽  
Intermediate Phenotypes ◽  
Gene Environment ◽  
Healthy Siblings

AbstractBackgroundFirst-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.MethodsWe conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.ResultsIn both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.ConclusionsThe degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

scholarly journals Predictive Performance of Exposome Score for Schizophrenia in the General Population

2020 ◽  
Author(s):  
Lotta-Katrin Pries ◽  
Gamze Erzin ◽  
Jim van Os ◽  
Margreet ten Have ◽  
Ron de Graaf ◽  
...  
Keyword(s):  
General Population ◽  
Characteristic Curve ◽  
Predictive Performance ◽  
Environment Interaction ◽  
Medical Outcomes ◽  
Cut Point ◽  
Schizophrenia Spectrum ◽  
Gene Environment ◽  
General Population Cohort ◽  
Discriminative Function

Abstract Previously, we established an estimated exposome score for schizophrenia (ES-SCZ) as a cumulative measure of environmental liability for schizophrenia to use in gene–environment interaction studies and for risk stratification in population cohorts. Hereby, we examined the discriminative function of ES-SCZ for identifying individuals diagnosed with schizophrenia spectrum disorder in the general population by measuring the area under the receiver operating characteristic curve (AUC). Furthermore, we compared this ES-SCZ method to an environmental sum score (Esum-SCZ) and an aggregate environmental score weighted by the meta-analytical estimates (Emet-SCZ). We also estimated ORs and Nagelkerke’s R2 for ES-SCZ in association with psychiatric diagnoses and other medical outcomes. ES-SCZ showed a good discriminative function (AUC = 0.84) and statistically significantly performed better than both Esum-SCZ (AUC = 0.80) and Emet-SCZ (AUC = 0.80). At optimal cut point, ES-SCZ showed similar performance in ruling out (LR− = 0.20) and ruling in (LR+ = 3.86) schizophrenia. ES-SCZ at optimal cut point showed also a progressively greater magnitude of association with increasing psychosis risk strata. Among all clinical outcomes, ES-SCZ was associated with schizophrenia diagnosis with the highest OR (2.76, P &lt; .001) and greatest explained variance (R2 = 14.03%), followed by bipolar disorder (OR = 2.61, P &lt; .001, R2 = 13.01%) and suicide plan (OR = 2.44, P &lt; .001, R2 = 12.44%). Our findings from an epidemiologically representative general population cohort demonstrate that an aggregate environmental exposure score for schizophrenia constructed using a predictive modeling approach—ES-SCZ—has the potential to improve risk prediction and stratification for research purposes and may help gain insight into the multicausal etiology of psychopathology.

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