scholarly journals Shared genetics and couple-associated environment are major contributors to the risk of both clinical and self-declared depression

2016 ◽  
Author(s):  
Yanni Zeng ◽  
Pau Navarro ◽  
Charley Xia ◽  
Carmen Amador ◽  
Ana M. Fernandez-Pujals ◽  
...  
Keyword(s):  
Environmental Effects ◽  
Genetic Variants ◽  
Environmental Effect ◽  
Genetic Effect ◽  
Health Department ◽  
Genetic Effects ◽  
Common Genetic Variants ◽  
Scottish Government ◽  
Family Based ◽  
Major Factors

AbstractBackgroundBoth genetic and environmental contributions to risk of depression have been identified, but estimates of their effects are limited. Commonalities between major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Dissecting the genetic and environmental contributions to these traits and their correlation would inform the design and interpretation of genetic studies.MethodsUsing data from a large Scottish family-based cohort (GS:SFHS, N=21,387), we estimated the genetic and environmental contributions to MDD and SDD. Genetic effects associated with common genome-wide genetic variants (SNP heritability) and additional pedigree-associated genetic variation and Non-genetic effects associated with common environments were estimated using linear mixed modeling (LMM).FindingsBoth MDD and SDD had significant contributions from effects of common genetic variants, the additional genetic effect of the pedigree and the common environmental effect shared by couples. The correlation between SDD and MDD was high (r=1⋅00, se=0⋅21) for common-variant-associated genetic effects and moderate for both the additional genetic effect of the pedigree (r=0⋅58, se=0⋅08) and the couple-shared environmental effect (r=0⋅53, se=0⋅22).InterpretationBoth genetics and couple-shared environmental effects were the major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression.FundingStudy supported by Wellcome Trust Strategic Award 104036/Z/14/Z. GS:SFHS funded by the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6.

scholarly journals Genetic and environmental contributions to psychological resilience and coping

2018 ◽  
Vol 3 ◽  
pp. 12 ◽  
Author(s):  
Lauren B Navrady ◽  
Yanni Zeng ◽  
Toni-Kim Clarke ◽  
Mark J Adams ◽  
David M Howard ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Coping Style ◽  
Genetic Correlations ◽  
Genetic Effects ◽  
Shared Environment ◽  
Psychological Resilience ◽  
Common Genetic Variants ◽  
Family Based ◽  
And Coping ◽  
Shared Environments

Background: Twin studies indicate that genetic and environmental factors contribute to both psychological resilience and coping style, but estimates of their relative molecular and shared environmental contributions are limited. The degree of overlap in the genetic architectures of these traits is also unclear. Methods: Using data from a large population- and family-based cohort Generation Scotland (N = 8,734), we estimated the genetic and shared environmental variance components for resilience, task-, emotion-, and avoidance-oriented coping style in a linear mixed model (LMM). Bivariate LMM analyses were used to estimate the genetic correlations between these traits. Resilience and coping style were measured using the Brief Resilience Scale and Coping Inventory for Stressful Situations, respectively. Results: The greatest proportion of the phenotypic variance in resilience remained unexplained, although significant contributions from common genetic variants and family-shared environment were found. Both task- and avoidance-oriented coping had significant contributions from common genetic variants, sibling- and couple-shared environments, variance in emotion-oriented coping was attributable to common genetic variants, family- and couple-shared environments. The estimated correlation between resilience and emotion-oriented coping was high for both common-variant-associated genetic effects (rG = -0.79, se = 0.19), and for the additional genetic effects from the pedigree (rK = -0.94, se = 0.30). Genetic correlations between resilience and task- and avoidance-oriented coping did not meet statistical significance. Conclusions: Both genetics and shared environmental effects were major contributing factors to coping style, whilst the variance in resilience remains largely unexplained. Strong genetic overlap between resilience and emotion-oriented coping suggests a relationship whereby genetic factors that increase negative emotionality also lead to decreased resilience. We suggest that genome-wide family-based studies of resilience and coping may help to elucidate tractable methodologies to identify genetic architectures and modifiable environmental risk factors to protect against psychiatric illness, although further work with larger sample sizes is needed.

scholarly journals Redefining tissue specificity of genetic regulation of gene expression in the presence of allelic heterogeneity

2021 ◽  
Author(s):  
Marios Arvanitis ◽  
Karl Tayeb ◽  
Benjamin J Strober ◽  
Alexis Battle
Keyword(s):  
Gene Expression ◽  
Genetic Variants ◽  
Tissue Specificity ◽  
Genetic Regulation ◽  
Regulation Of Gene Expression ◽  
Genetic Effects ◽  
Allelic Heterogeneity ◽  
Common Genetic Variants ◽  
Causal Variants ◽  
Disease Loci

Understanding the mechanisms that underlie genetic regulation of gene expression is crucial to explaining the diversity that governs complex traits. Large scale expression quantitative trait locus (eQTL) studies have been instrumental in identifying genetic variants that influence the expression of target genes. However, a large fraction of disease-associated genetic variants have not been clearly explained by current eQTL data, frustrating attempts to use these data to comprehensively characterize disease loci. One notable observation from recent studies is that cis-eQTL effects are often shared across different cell types and tissues. This would suggest that common genetic variants impacting steady-state, adult gene expression are largely tolerated, shared across tissues, and less relevant to disease. However, allelic heterogeneity and complex patterns of linkage disequilibrium (LD) within each locus may skew the quantification of sharing of genetic effects between tissues, impede our ability to identify causal variants, and hinder the identification of regulatory effects for disease-associated genetic variants. Indeed, recent research suggests that multiple causal variants are often present in many eQTL and complex trait associated loci. Here, we re-analyze tissue-specificity of genetic effects in the presence of LD and allelic heterogeneity, proposing a novel method, CAFEH, that improves the identification of causal regulatory variants across tissues and their relationship to disease loci.

scholarly journals Consortium genome-wide meta-analysis for childhood dental caries traits

2017 ◽  
Author(s):  
Simon Haworth ◽  
Dmitry Shungin ◽  
Justin T van der Tas ◽  
Strahinja Vucic ◽  
Carolina Medina Gomez ◽  
...  
Keyword(s):  
Dental Caries ◽  
Genetic Variants ◽  
Primary Teeth ◽  
Meta Analysis ◽  
Genetic Effects ◽  
Permanent Dentition ◽  
Permanent Teeth ◽  
Common Disease ◽  
Genome Wide ◽  
Common Genetic Variants

AbstractPrior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from 9 contributing centers. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage (imputed to Haplotype Reference Consortium or 1000 Genomes phase 1 version 3 panels) accounting for population stratification. Fixed–effects meta-analysis was performed weighted by inverse standard error. Analysis included up to 19,003 individuals (7,530 affected) for primary teeth and 13,353 individuals (5,875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth (intronic within ALLC, Odds Ratio (OR) 0.85, Effect Allele Frequency (EAF) 0.60, p 4.13e-8) and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, p 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low (h2 of 1% [95% CI: 0%:7%] and 6% [95% CI 0%:13%] for primary and permanent dentitions, respectively) compared to corresponding within-study estimates (h2 of 28%, [95% CI: 9%:48%] and 17% [95% CI:2%:31%]) or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.Author summaryDental caries (tooth decay) is a common disease in children. Previous studies suggest genetic factors alter caries risk, but to date there is a gap of knowledge in identifying which specific genetic variants are responsible. We undertook analysis in a consortium including around 19,000 children and investigated whether any of 8 million common genetic variants were associated with risk of caries in primary (milk) or permanent teeth. If identified, these variants are used as ‘tags’ to highlight genes which may be involved in a disease. We identified variants in two loci associated with caries status; in the primary (rs1594318) and permanent dentition (rs7738851). The former is intronic in ALLC, a gene with poorly understood function. The latter is an intronic variant within NEDD9, a gene which has several known functions including a role in development of craniofacial structures. To gain a more comprehensive understanding of genetic effects which influence caries larger studies and a better understanding of environmental modifiers or interactions with genetic effects are required.

Do schooling gains yield anomalous Jensen effects? A reply to Flynn (2019) including a meta-analysis

2019 ◽  
Vol 51 (6) ◽  
pp. 917-919
Author(s):  
Jan te Nijenhuis ◽  
Esteban van der Boor ◽  
Yu Yong Choi ◽  
Kunho Lee
Keyword(s):  
Environmental Effects ◽  
Environmental Effect ◽  
Meta Analysis ◽  
Thought Experiments ◽  
Real Data ◽  
Genetic Effects ◽  
Diagnostic Instrument ◽  
Meta Analyses

AbstractA test of Jensen effects is of nil value as a diagnostic instrument when various good-sized meta-analyses show Jensen effects appear for both genetic effects and environmental effects. Using thought experiments, Flynn (2019) claims that some schooling gains yield Jensen effects, which should not be the case for an environmental effect. However, a meta-analysis (K = 12, total N = 60,993, mean r = 0.13) of schooling gains shows no Jensen effect. Real data trump thought experiments, so it is concluded there is no empirical proof of anomalous Jensen effects for schooling gains.

scholarly journals Threshold trait architecture of Hsp90-buffered variation

2015 ◽  
Author(s):  
Charles C Carey ◽  
Kristen F Gorman ◽  
Becky Howsmon ◽  
Charles Kooperberg ◽  
Aaron K Aragaki ◽  
...  
Keyword(s):  
Environmental Effects ◽  
Artificial Selection ◽  
Genetic Variants ◽  
Genome Mapping ◽  
Whole Genome ◽  
Threshold Trait ◽  
Common Genetic Variants ◽  
Underlying Basis ◽  
Whole Genome Mapping ◽  
Control Genotype

Common genetic variants buffered by Hsp90 are candidates for human diseases of signaling such as cancer. Like cancer, morphological abnormalities buffered by Hsp90 are discrete threshold traits with a continuous underlying basis of liability determining their probability of occurrence. QTL and deletion maps for one of the most frequent Hsp90-dependent abnormalities in Drosophila, deformed eye (dfe), were replicated across three genetically related artificial selection lines using strategies dependent on proximity to the dfe threshold and the direction of genetic and environmental effects. Up to 17 dfe loci (QTL) linked by 7 interactions were detected based on the ability of small recombinant regions of an unaffected and completely homozygous control genotype to dominantly suppress or enhance dfe penetrance at its threshold in groups of isogenic recombinant flies, and over 20 deletions increased dfe penetrance from a low expected value in one or more line, identifying a complex network of genes responsible for the dfe phenotype. Replicated comparisons of these whole-genome mapping approaches identified several QTL regions narrowly defined by deletions and 4 candidate genes, with additional uncorrelated QTL and deletions highlighting differences between the approaches and the need for caution in attributing the effect of deletions directly to QTL genes.

Genetic and environmental effects on isometric muscle strength and leg extensor power followed up for three years among older female twins

2009 ◽  
Vol 106 (5) ◽  
pp. 1604-1610 ◽  
Author(s):  
Kristina Tiainen ◽  
Sarianna Sipilä ◽  
Markku Kauppinen ◽  
Jaakko Kaprio ◽  
Taina Rantanen
Keyword(s):  
Muscle Strength ◽  
Environmental Effects ◽  
Muscle Power ◽  
Knee Extensor ◽  
Genetic Effect ◽  
Genetic Effects ◽  
Time Specific ◽  
Leg Extensor Power ◽  
Isometric Muscle

The purpose of this study was to examine changes in the contribution of genetic and environmental effects to isometric knee extensor strength and leg extensor power among 63- to 76-year-old female twins over a 3-yr follow-up. At baseline in 2000 the sample comprised 206 monozygotic (MZ) and 228 dizygotic (DZ) twin individuals, and at follow-up in 2003 the sample comprised 149 MZ and 164 DZ twin individuals. Genetic modeling showed that genetic effects explained 58% (95% CI: 46–68%) of the variance in muscle strength at baseline and 56% (95% CI: 41–68%) at follow-up, with no occasion-specific genetic effect. Nonshared environmental effects accounted for 42% (95% CI: 32–54%) of the variation at baseline and 15% (95% CI: 7–26%) at follow-up. In addition, new nonshared environmental effects explained the remaining variance, 29% (95% CI: 22–37%) of muscle strength at follow-up. For muscle power, the same genetic effects accounted for 67% (95% CI: 57–74%) of the variation at baseline and 48% (95% CI: 34–61%) at follow-up. Nonshared environmental effects in common at both measurement points explained 33% (95% CI: 25–43%) of the total variation at baseline and 11% (95% CI: 5–21%) at follow-up. The remaining variance of muscle power at follow-up was accounted for by time-specific environmental effects. Results indicated that the contribution of genetic effects to isometric muscle strength was stable, whereas for leg extensor power the proportion of genetic effects decreased during the follow-up. We observed new specific environmental effects underlying follow-up muscle strength and power, which effects could be due to the onset of new disease processes or changes in lifestyle.

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

Personal Goals of Older Female Twins

2009 ◽  
Vol 14 (2) ◽  
pp. 160-167 ◽  
Author(s):  
Katariina Salmela-Aro ◽  
Sanna Read ◽  
Jari-Erik Nurmi ◽  
Markku Koskenvuo ◽  
Jaakko Kaprio ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Independent Living ◽  
Environmental Effect ◽  
Close Relationships ◽  
Environmental Influence ◽  
Genetic Effect ◽  
Additive Genetic Effect ◽  
Personal Goals ◽  
Cultural Activities ◽  
The Individual

This study examined genetic and environmental influences on older women’s personal goals by using data from the Finnish Twin Study on Aging. The interview for the personal goals was completed by 67 monozygotic (MZ) pairs and 75 dizygotic (DZ) pairs. The tetrachoric correlations for personal goals related to health and functioning, close relationships, and independent living were higher in MZ than DZ twins, indicating possible genetic influence. The pattern of tetrachoric correlations for personal goals related to cultural activities, care of others, and physical exercise indicated environmental influence. For goals concerning health and functioning, independent living, and close relationships, additive genetic effect accounted for about half of the individual variation. The rest was the result of a unique environmental effect. Goals concerning physical exercise and care of others showed moderate common environmental effect, while the rest of the variance was the result of a unique environmental effect. Personal goals concerning cultural activities showed unique environmental effects only.

Sign in / Sign up

Export Citation Format

Share Document