Interpersonal childhood adversity and stress generation in adolescence: Moderation by HPA axis multilocus genetic variation

2019 ◽  
Vol 32 (3) ◽  
pp. 865-878 ◽  
Author(s):  
Meghan Huang ◽  
Lisa R. Starr
Keyword(s):  
Genetic Variation ◽  
Hpa Axis ◽  
Childhood Adversity ◽  
Stress Generation ◽  
Genetic Profile ◽  
Environment Interaction ◽  
Interpersonal Stress ◽  
Nucleotide Polymorphisms ◽  
Wide Range ◽  
Profile Score

AbstractResearch suggests that childhood adversity (CA) is associated with a wide range of repercussions, including an increased likelihood of interpersonal stress generation. This may be particularly true following interpersonal childhood adversity (ICA) and for youth with high hypothalamic-pituitary-adrenal (HPA) axis-related genetic risk. In the current study, we applied a multilocus genetic profile score (MGPS) approach to measuring HPA axis-related genetic variation and examined its interaction with ICA to predict interpersonal stress generation in a sample of adolescents aged 14–17 (N = 241, Caucasian subsample n = 192). MGPSs were computed using 10 single nucleotide polymorphisms from HPA axis-related genes (CRHR1, NRC31, NRC32, and FKBP5). ICA significantly predicted greater adolescent interpersonal dependent stress. Additionally, MGPS predicted a stronger association between ICA and interpersonal dependent (but not independent or noninterpersonal dependent) stress. No gene–environment interaction (G×E) effects were found for noninterpersonal CA and MGPS in predicting adolescent interpersonal dependent stress. Effects remained after controlling for current depressive symptoms and following stratification by race. Findings extend existing G×E research on stress generation to HPA axis-related genetic variation and demonstrate effects specific to the interpersonal domain.

Stress sensitization to depression following childhood adversity: Moderation by HPA axis and serotonergic multilocus profile scores

2020 ◽  
pp. 1-15
Author(s):  
Lisa R. Starr ◽  
Catherine B. Stroud ◽  
Zoey A. Shaw ◽  
Suzanne Vrshek-Schallhorn
Keyword(s):  
Genetic Variation ◽  
Life Events ◽  
Hpa Axis ◽  
Life Stress ◽  
Childhood Adversity ◽  
Risk Scores ◽  
Genetic Profile ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Stress Sensitization

Abstract Childhood adversity appears to sensitize youth to stress, increasing depression risk following stressful life events occurring throughout the lifespan. Some evidence suggests hypothalamic–pituitary–adrenal (HPA) axis-related and serotonergic genetic variation moderates this effect, in a “gene-by-environment-by-environment” interaction (G × E × E). However, prior research has tested single genetic variants, limiting power. The current study uses a multilocus genetic profile score (MGPS) approach to capture polygenic risk relevant to HPA axis and serotonergic functioning. Adolescents (N = 241, Mage = 15.90) completed contextual-threat-based interviews assessing childhood adversity and acute life events, and diagnostic interviews assessing depression. Established MGPSs indexed genetic variation linked to HPA axis (10 single nucleotide polymorphisms [SNPs]) and serotonergic (five SNPs) functioning. Results showed significant MGPS × Childhood Adversity × Recent Life Stress interactions predicting depression for both HPA axis and serotonergic MGPSs, with both risk scores predicting stronger Childhood Adversity × Recent Stress interactions. Serotonergic genetic risk specifically predicted sensitization to major interpersonal stressors. The serotonergic MGPS G × E × E was re-tested in an independent replication sample of early adolescent girls, with comparable results. Findings support the notion that genetic variation linked to these two neurobiological symptoms alters stress sensitization, and that gene-by-environment (G × E) interactions may be qualified by environmental exposures occurring at different points in development.

scholarly journals HPA axis multilocus genetic profile score moderates the impact of interpersonal stress on prospective increases in depressive symptoms for offspring of depressed mothers.

2017 ◽  
Vol 126 (8) ◽  
pp. 1017-1028 ◽  
Author(s):  
Cope Feurer ◽  
John E. McGeary ◽  
Valerie S. Knopik ◽  
Leslie A. Brick ◽  
Rohan H. Palmer ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Hpa Axis ◽  
Genetic Profile ◽  
Interpersonal Stress ◽  
Profile Score ◽  
Depressed Mothers ◽  
The Impact

HPA-axis multilocus genetic variation moderates associations between environmental stress and depressive symptoms among adolescents

2018 ◽  
Vol 31 (04) ◽  
pp. 1339-1352 ◽  
Author(s):  
Lisa R. Starr ◽  
Meghan Huang
Keyword(s):  
Genetic Variation ◽  
Depressive Symptoms ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Acute Stress ◽  
Childhood Adversity ◽  
Genetic Profile ◽  
Acute And Chronic Stress ◽  
Adolescent Depressive Symptoms ◽  
Gene Environment

AbstractResearch suggests that genetic variants linked to hypothalamic-pituitary-adrenal (HPA)-axis functioning moderate the association between environmental stressors and depression, but examining gene–environment interactions with single polymorphisms limits power. The current study used a multilocus genetic profile score (MGPS) approach to measuring HPA-axis–related genetic variation and examined interactions with acute stress, chronic stress, and childhood adversity (assessed using contextual threat interview methods) with depressive symptoms as outcomes in an adolescent sample (ages 14–17, N = 241; White subsample n = 192). Additive MGPSs were calculated using 10 single nucleotide polymorphisms within HPA-axis genes (CRHR1, NR3C2, NR3C1, FKBP5). Higher MGPS directly correlated with adolescent depressive symptoms. Moreover, MGPS predicted stronger associations between acute and chronic stress and adolescent depressive symptoms and also moderated the effect of interpersonal, but not noninterpersonal, childhood adversity. Gene–environment interactions individually accounted for 5%–8% of depressive symptom variation. All results were retained following multiple test correction and stratification by race. Results suggest that using MGPSs provides substantial power to examine gene–environmental interactions linked to affective outcomes among adolescents.

scholarly journals Rapid climate-driven evolution of the invasive species Mytilus galloprovincialis over the past century

2020 ◽  
Vol 3 (1) ◽  
pp. 14-29
Author(s):  
Guo-Dong Han ◽  
Yun-Wei Dong
Keyword(s):  
Invasive Species ◽  
Genetic Variation ◽  
Mytilus Galloprovincialis ◽  
Climatic Factors ◽  
Northwestern Pacific ◽  
Past Century ◽  
Nucleotide Polymorphisms ◽  
Adaptive Genetic Variation ◽  
The Past ◽  
Wide Range

Climate-driven adaptive genetic variation is one of the most important ways for organisms to tolerate environmental change and succeed in altered environments. To understand rapid climate-driven evolution, and how this evolution might shift biogeographic distributions in response to global change, we measured the adaptive genetic variation to the local environment of a marine invasive species Mytilus galloprovincialis. The genetic structure of eight populations from the Mediterranean Sea, northeastern Atlantic, northeastern Pacific, and northwestern Pacific were determined using genome-wide screens for single nucleotide polymorphisms. The relationships of genetic variation to environmental (seawater and air) temperature were analyzed using redundancy analysis and BayeScEnv analysis to evaluate the impacts of temperature on the genetic divergences among these eight populations. We found that the genetic compositions were significantly different among populations and the adaptive genetic variation was associated with temperature variables. Further, we identified some genetic markers exhibiting signatures of divergent selection in association with environmental features that can be used in the future to closely monitor adaptive variation in this species. Our results suggest that divergent climatic factors have driven adaptive genetic variation in M. galloprovincialis over the past century. The rapid evolutionary adaptation has played a pivotal role in enabling this species to invade a wide range of thermal habitats successfully. Species like M. galloprovincialis that possess high levels of genetic variation may not only be especially capable of invading new habitats with different environmental conditions, but also poised to cope rapidly and successfully with rising global temperatures.

scholarly journals HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood

2020 ◽  
pp. 1-13 ◽  
Author(s):  
Brooke G. McKenna ◽  
Constance Hammen ◽  
Patricia A. Brennan
Keyword(s):  
Perceived Stress ◽  
Hpa Axis ◽  
Fetal Programming ◽  
Genetic Risk ◽  
Maternal Stress ◽  
Early Adulthood ◽  
Genetic Profile ◽  
Polygenic Risk ◽  
Profile Score ◽  
Prospective Longitudinal

Abstract Maternal stress during pregnancy can cause alterations to the fetal hypothalamus–pituitary–adrenal (HPA) axis, a phenomenon known as fetal programming that may have lasting effects on offspring outcomes, including depression. Evidence suggests that these effects may vary with respect to the offspring's genetic risk. Nonetheless, few studies have examined these effects into adulthood, when risk for depression onset is highest. The present study builds upon the extant literature by examining the interaction of maternal prenatal perceived stress (MPPS) and offspring HPA-axis polygenic risk to predict offspring depression in early adulthood. A total of 381 mother–child dyads participated in a prospective, longitudinal study that spanned from pregnancy until offspring were 20 years of age. Polygenic risk was defined by a multilocus genetic profile score (MGPS) that reflected the additive risk of three HPA-axis candidate genes. The results indicated that the interaction of MPPS and HPA-axis MGPS confers risk for offspring depression at age 20, in line with the differential susceptibility model. This interaction may be specific to prenatal stress, as maternal stress during early childhood did not interact with genetic risk to predict depression. These findings provide the first evidence that genetic variants that are associated with the HPA axis may act in a polygenic, additive fashion to moderate the association between fetal programming and adult depression.

scholarly journals Genetic Variation in the Visfatin Gene (PBEF1) and Its Relation to Glucose Metabolism and Fat-Depot-Specific Messenger Ribonucleic Acid Expression in Humans

2006 ◽  
Vol 91 (7) ◽  
pp. 2725-2731 ◽  
Author(s):  
Yvonne Böttcher ◽  
Daniel Teupser ◽  
Beate Enigk ◽  
Janin Berndt ◽  
Nora Klöting ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Fat Distribution ◽  
Minor Effect ◽  
Nucleotide Polymorphisms ◽  
Association Analyses ◽  
Messenger Ribonucleic Acid ◽  
Fat Depots ◽  
Wide Range

Abstract Context and Objective: Visfatin is a peptide suggested to play a role in glucose homeostasis. In the present study, we investigated the role of genetic variation in the visfatin gene in the pathophysiology of obesity/type 2 diabetes mellitus (T2DM). Design: The visfatin gene (PBEF1) was sequenced in DNA samples from 24 nonrelated Caucasian subjects. Identified genetic variants were used for association analyses of T2DM in a case-control study (503 diabetic subjects and 476 healthy controls) and T2DM-related traits in 626 nondiabetic subjects. The effect of genetic variation in the visfatin gene on its mRNA expression in a subgroup of 157 nondiabetic subjects with measurements of visfatin mRNA expression in visceral and sc fat depots was also analyzed. Results: Seven single-nucleotide polymorphisms (SNPs) and one insertion/deletion were identified. Three SNPs (rs9770242, −948G→T, rs4730153) that were representatives of their linkage disequilibrium groups were genotyped in Caucasians from Germany with a wide range of body fat distribution and insulin sensitivity for association analyses. No association of T2DM with any of the genotyped SNPs or their haplotypes was found. However, the ratio of visceral/sc visfatin mRNA expression was associated with all three genetic polymorphisms (P < 0.05). Moreover, the −948G→T variant was associated with 2-h plasma glucose and fasting insulin concentrations (P < 0.05) in nondiabetic subjects. Conclusions: In conclusion, our data suggest that genetic variation in the visfatin gene may have a minor effect on visceral and sc visfatin mRNA expression profiles but does not play a major role in the development of obesity or T2DM.

scholarly journals Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Melisa Intan Barliana ◽  
Arif Satria Wira Kusuma ◽  
Widya Norma Insani ◽  
Sofa Dewi Alfian ◽  
Ajeng Diantini ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Drug Transport ◽  
Population Data ◽  
Cross Sectional Study ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Hardy Weinberg Equilibrium ◽  
Tuberculosis Therapy ◽  
Genetic Profiles

Abstract Objective The risk of contracting tuberculosis (TB) and the efficacy of TB therapy are affected by several factors, including genetic variation among populations. In the Indonesian population, data on the genes involved in drug transport and metabolism of TB therapy are limited. The aim of this study was to identify the genetic profile of the ABCB1 gene (rs1128503 and rs1045642) and CYP2E1 gene (rs3813867) in Indonesians with TB. This study was a cross-sectional study of 50 TB outpatients in Jambi city, Indonesia. Sociodemographic characteristics were obtained from medical records. Whole blood was collected, and genomic DNA was isolated. Single nucleotide polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism with HaeIII, MboI, and PstI for rs1128503, rs1045642 (ABCB1), and rs3813867 (CYP2E1), respectively. Result The frequency of alleles of each gene was analyzed by Hardy–Weinberg equilibrium. The genetic profiles of ABCB1 rs1128503 and rs1045642 were varied (CC, CT, TT), while CYP2E1 rs3813867 was present in CC (wild type). The genetic variations of ABCB1 and CYP2E1 may have no significant correlation with the duration of TB therapy. Nevertheless, this study may provide as preliminary results for the genetic profiles of ABCB1 (rs1128503, rs1045642) and CYP2E1 (rs3813867) in the Indonesia population.

scholarly journals Genetic variation in the hypothalamic–pituitary–adrenal stress axis influences susceptibility to musculoskeletal pain: results from the EPIFUND study

2009 ◽  
Vol 69 (3) ◽  
pp. 556-560 ◽  
Author(s):  
Kate L Holliday ◽  
Barbara I Nicholl ◽  
Gary J Macfarlane ◽  
Wendy Thomson ◽  
Kelly A Davies ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Musculoskeletal Pain ◽  
Hpa Axis ◽  
Negative Binomial ◽  
Chronic Widespread Pain ◽  
Stress Axis ◽  
Poor Sleep ◽  
Nucleotide Polymorphisms ◽  
Hypothalamic Pituitary Adrenal ◽  
Time Points

ObjectivesTo determine if genetic variation in genes in the hypothalamic–pituitary–adrenal (HPA) axis, the primary stress response system, influences susceptibility to developing musculoskeletal pain.MethodsPain and comorbidity data was collected at three time points in a prospective population-based cohort study. Pairwise tagging single nucleotide polymorphisms (SNPs) were selected and genotyped for seven genes. Genetic association analysis was carried out using zero-inflated negative binomial regression to test for association between SNPs and the maximum number of pain sites across the three time points in participants reporting pain, reported as proportional changes with 95% CIs. SNPs were also tested for association with chronic widespread pain (CWP) using logistic regression reporting odds ratios and 95% CI.ResultsA total of 75 SNPs were successfully genotyped in 994 participants including 164 cases with persistent CWP and 172 pain-free controls. Multiple SNPs in SERPINA6 were associated with the maximum number of pain sites; for example, each copy of the T allele of rs941601 was associated with having 16% (proportional change=1.16, 95% CI 1.04 to 1.28, p=0.006) more pain sites compared to participants with the CC genotype. SERPINA6 gene SNPs were also associated with CWP. Significant associations between the maximum number of pain sites and SNPs in the CRHBP and POMC genes were also observed and a SNP in MC2R was also associated with CWP. Associations between SNPs and comorbidity of poor sleep quality and depression explained some of the associations observed.ConclusionsGenetic variation in HPA axis genes was associated with musculoskeletal pain; however, some of the associations were explained by comorbidities. Replication of these findings is required in independent cohorts.

Maintenance of Quantitative Genetic Variation

2018 ◽  
Author(s):  
Bruce Walsh ◽  
Michael Lynch
Keyword(s):  
Genetic Variation ◽  
Quantitative Genetics ◽  
Stabilizing Selection ◽  
Quantitative Genetic ◽  
Wide Range

One of the major unresolved issues in quantitative genetics is what accounts for the amount of standing genetic variation in traits. A wide range of models, all reviewed in this chapter, have been proposed, but none fit the data, either giving too much variation or too little apparent stabilizing selection.

scholarly journals Genomic Analyses of Globodera pallida, A Quarantine Agricultural Pathogen in Idaho

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 363
Author(s):  
Sulochana K. Wasala ◽  
Dana K. Howe ◽  
Louise-Marie Dandurand ◽  
Inga A. Zasada ◽  
Dee R. Denver
Keyword(s):  
Genetic Variation ◽  
Potato Production ◽  
Globodera Pallida ◽  
Fixation Index ◽  
Parasitic Nematodes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Field Samples ◽  
Multiple Introduction

Globodera pallida is among the most significant plant-parasitic nematodes worldwide, causing major damage to potato production. Since it was discovered in Idaho in 2006, eradication efforts have aimed to contain and eradicate G. pallida through phytosanitary action and soil fumigation. In this study, we investigated genome-wide patterns of G. pallida genetic variation across Idaho fields to evaluate whether the infestation resulted from a single or multiple introduction(s) and to investigate potential evolutionary responses since the time of infestation. A total of 53 G. pallida samples (~1,042,000 individuals) were collected and analyzed, representing five different fields in Idaho, a greenhouse population, and a field in Scotland that was used for external comparison. According to genome-wide allele frequency and fixation index (Fst) analyses, most of the genetic variation was shared among the G. pallida populations in Idaho fields pre-fumigation, indicating that the infestation likely resulted from a single introduction. Temporal patterns of genome-wide polymorphisms involving (1) pre-fumigation field samples collected in 2007 and 2014 and (2) pre- and post-fumigation samples revealed nucleotide variants (SNPs, single-nucleotide polymorphisms) with significantly differentiated allele frequencies indicating genetic differentiation. This study provides insights into the genetic origins and adaptive potential of G. pallida invading new environments.

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