This study aimed to understand the potassium voltage-gated channel KQT-like subfamily, member 1 gene polymorphism in a rural elderly population in a county in Guangxi and to explore the possible relationship between its gene polymorphism and blood sugar. The 6 SNP loci of blood DNA samples from 4355 individuals were typed using the imLDRTM Multiple SNP Typing Kit from Shanghai Tianhao Biotechnology Co. The data combining epidemiological information (baseline questionnaire and physical examination results) and genotyping results were statistically analyzed using GMDR0.9 software and SPSS22.0 software. A total of 4355 elderly people aged 60 years and above were surveyed in this survey, and the total abnormal rate of glucose metabolism was 16·11 % (699/4355). Among them, male:female ratio was 1:1·48; the age group of 60–69 years old accounted for the highest proportion, with 2337 people, accounting for 53·66 % (2337/4355). The results of multivariate analysis showed that usually not doing farm work (OR 1·26; 95 % CI 1·06, 1·50), TAG ≥ 1·70 mmol/l (OR 1·19; 95 % CI 1·11, 1·27), hyperuricaemia (OR 1·034; 95 % CI 1·01, 1·66) and BMI ≥ 24 kg/m2 (OR 1·06; 95 % CI 1·03, 1·09) may be risk factors for abnormal glucose metabolism. Among all participants, rs151290 locus AA genotype, A allele carriers (AA+AC) were 0.70 times more likely (0.54 to 0.91) and 0.82 times more likely (0.70 to 0.97) to develop abnormal glucose metabolism than CC genotype carriers, respectively. Carriers of the T allele at the rs2237892 locus (CT+TT) were 0.85 times more likely to have abnormal glucose metabolism than carriers of the CC genotype (0.72 to 0.99); rs2237897 locus CT gene. The possibility of abnormal glucose metabolism in the carriers of CC genotype, TT genotype and T allele (CT + TT) is 0·79 times (0·67–0·94), 0·74 times (0·55–0·99) and 0·78 times (0·66, 0·92). The results of multifactor dimensionality reduction showed that the optimal interaction model was a three-factor model consisting of farm work, TAG and rs2237897. The best model dendrogram found that the interaction between TAG and rs2237897 had the strongest effect on fasting blood glucose in the elderly in rural areas, and they were mutually antagonistic. Environment–gene interaction is an important factor affecting abnormal glucose metabolism in the elderly of a county in Hechi City, Guangxi.

Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene–environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.

Child genotype is an important biologically based individual difference conferring differential sensitivity to the effect of parental behavior. This study explored dopaminergic polygenic composite × parental behavior interactions in relation to young children’s executive function. Participants were 135 36-month-old children and their mothers drawn from a prospective cohort followed longitudinally from pregnancy. A polygenic composite was created based on the number of COMT, DAT1, DRD2, and DRD4 alleles associated with increased reward sensitivity children carried. Maternal negative reactivity and responsiveness were coded during a series of structured mother–child interactions. Executive function was operationalized as self-control and working memory/inhibitory control. Path analysis supported a polygenic composite by negative reactivity interaction for self-control. The nature of the interaction was one of diathesis-stress, such that higher negative reactivity was associated with poorer self-control for children with higher polygenic composite scores. This result suggests that children with a higher number of alleles may be more vulnerable to the negative effect of negative reactivity. Negative reactivity may increase the risk for developing behavior problems in this population via an association with poorer self-control. Due to the small sample size, these initial findings should be treated with caution until they are replicated in a larger independent sample.

Behavioral genetics and cultural evolution have both revolutionized our understanding of human behavior – largely independent of each other. Here, we reconcile these two fields under a dual inheritance framework, offering a more nuanced understanding of the interaction between genes and culture. Going beyond typical analyses of gene–environment interactions, we describe the cultural dynamics that shape these interactions by shaping the environment and population structure. A cultural evolutionary approach can explain, for example, how factors such as rates of innovation and diffusion, density of cultural subgroups, and tolerance for behavioral diversity impact heritability estimates, thus yielding predictions for different social contexts. Moreover, when cumulative culture functionally overlaps with genes, genetic effects become masked, unmasked, or even reversed, and the causal effects of an identified gene become confounded with features of the cultural environment. The manner of confounding is specific to a particular society at a particular time, but a WEIRD (western, educated, industrialized, rich, and democratic) sampling problem obscures this boundedness. Cultural evolutionary dynamics are typically missing from models of gene-to-phenotype causality, hindering generalizability of genetic effects across societies and across time. We lay out a reconciled framework and use it to predict the ways in which heritability should differ between societies, between socioeconomic levels, and other groupings within some societies but not others, and over the life course. An integrated cultural evolutionary behavioral genetic approach cuts through the nature–nurture debate and helps resolve controversies in topics such as IQ.

The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.

The association between childhood adversity (CA) and psychosis has been extensively investigated in recent years. An increasing body of research has also focused on the mediating or moderating role of biological and psychological mechanisms, as well as other risk factors that might account for the link between CA and psychosis. We conducted a systematic search of the PsychINFO, Embase, Ovid, and Web of Science databases for original articles investigating the role of genetic vulnerabilities, environmental factors, psychological and psychopathological mechanisms in the association between CA and psychosis up to August 2019. We included studies with individuals at different stages of the psychosis continuum, from subclinical psychotic experiences to diagnosed disorders. From the 28 944 records identified, a total of 121 studies were included in this review. Only 26% of the studies identified met the criteria for methodological robustness. Overall, the current evidence suggests that CA may be associated with psychosis largely independently of genetic vulnerabilities. More consistent and robust evidence supports interaction between early and recent adversities, as well as the mediating role of attachment and mood symptoms, which is suggestive of an affective pathway between CA and psychosis across the continuum from subclinical experiences to diagnosable disorder. This review highlighted numerous methodological issues with the existing literature, including selection bias, heterogeneity of measurement instruments utilised, and lack of control for potential confounders. Future research should address these limitations to more accurately estimate mediation and moderation effects on the CA-psychosis association to inform the development of preventive interventions.

The study and identification of genotype–environment interactions (GxE) has been a hot topic in the field of human genetics for several decades. Yet the extent to which GxE contributes to human behavior variability, and its mechanisms, remains largely unknown. Nick Martin has contributed important advances to the field of GxE for human behavior, which include methodological developments, novel analyses and reviews. Here, we will first review Nick’s contributions to the GxE research, which started during his PhD and consistently appears in many of his over 1000 publications. Then, we recount a project that led to an article testing the diathesis-stress model for the origins of depression. In this publication, we observed the presence of an interaction between polygenic risk scores for depression (the risk in our ‘genotype’) and stressful life events (the experiences from our ‘environment’), which provided the first empirical support of this model.

Schizophrenia is a severe mental disorder striking mainly young adults and leading to life-long disability in a substantial portion of the sufferers. On the other hand, substantial knowledge about its etiology and pathogenesis is still lacking. Therefore the European Science Foundation (ESF) sponsored a meeting of a panel of European experts on schizophrenia research to discuss the state of art and future perspectives of key topics in this area. The fields covered genetics, epidemiology, animal models, molecular neuropathology and imaging. This was a first step to establish a network of European groups dedicated to Schizophrenia research. The coming calls of the frame work program will be used to strengthen this network in order to achieve substantial progress in understanding and treating this devastating illness.

Research 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.

Lead is one of the environmental pollutants with cardiovascular toxicity. The embryos are particularly sensitive to lead exposure, because it can move through the blood-placental barrier and the blood-brain barrier easily during embryonic development. Cerebral cavernous malformations 3 (CCM3) gene plays an important role in cardiovascular development, mainly affecting cell proliferation, differentiation and apoptosis. In this study, we established a blood vessel development model of mouse embryos in order to imitate human people with CCM3 genes defects and exposing to environment toxin Pb in utero. We would like to determine the interaction of Pb and CCM3 gene on vascular development, and to explore the mechanisms. We found that the yolk sac of CCM3 heterozygous mice embryo showed abnormal morphology at E11.5 after lead treatment comparing with wild type (WT) mice without lead exposure, meanwhile it showed more angiogenesis and vascular remodeling in the hematoxylin and eosin stained sections of the CCM3+/− yolk sac with lead exposure. We also found that the similar effect of Pb and CCM3 gene on mitochondrial DNA (mtDNA) copy number in vivo and in vitro. Mitochondrial morphology and function also changed in primary human umbilical vein endothelial cells after lead exposure. Besides, it was found that the HIF-1α and TFAM which have close relationship with mtDNA biogenesis showed similarly increasing messenger RNA expression in both human and mouse-derived primary cells with lead treated and CCM3 gene knockout. All of the above results indicated that lead and CCM3 might damage endothelial cells through mitochondria pathway and eventually both affected angiogenesis.

In this paper, I explore in an overlapping generations framework, a mechanism motivating a neurobiological poverty trap. Poverty causes stress and depression in individuals susceptible to depression. Poor and depressed individuals discount the future at a higher rate and invest less in the human capital of their children than mentally healthy or rich individuals. This gene–environment interaction generates a vicious cycle in which poor individuals inherit not only susceptibility to depression, but also stress and poverty. I show that a successful one-time intervention has the power to permanently eliminate the neurobiological poverty trap.

Body mass and fat intake are multifactorial traits that have genetic and environmental components. The gene with the greatest effect on body mass is FTO (fat mass and obesity-associated), but several studies have shown that the effect of FTO (and of other genes) on body mass can be modified by the intake of nutrients. The so-called gene–environment interactions may also be important for the effectiveness of weight-loss strategies. Food choices, and thus fat intake, depend to some extent on individual preferences. The most important biological component of food preference is taste, and the role of fat sensitivity in fat intake has recently been pointed out. Relatively few studies have analysed the genetic components of fat intake or fatty acid sensitivity in terms of their relation to obesity. It has been proposed that decreased oral fatty acid sensitivity leads to increased fat intake and thus increased body mass. One of the genes that affect fatty acid sensitivity is CD36 (cluster of differentiation 36). However, little is known so far about the genetic component of fat sensing. We performed a literature review to identify the state of knowledge regarding the genetics of fat intake and its relation to body-mass determination, and to identify the priorities for further investigations.

Objectives: To examine whether apolipoprotein e4 (APOE) status moderates the association of family environment with child functioning following early traumatic brain injury (TBI). Methods: Sixty-five children with moderate to severe TBI and 70 children with orthopedic injury (OI) completed assessments 6, 12, 18 months, and 3.5 and 6.8 years post injury. DNA was extracted from saliva samples and genotyped for APOE e4 status. Linear mixed models examined moderating effects of APOE e4 status on associations between two family environment factors (parenting style, home environment) and three child outcomes (executive functioning, behavioral adjustment, adaptive functioning). Results: Children with TBI who were carriers of the e4 allele showed poorer adaptive functioning relative to non-carriers with TBI and children with OI in the context of low authoritarianism. At high levels of authoritarianism, non-carriers with TBI showed the poorest adaptive functioning among groups. There were no main effects or interactions involving APOE and executive functioning or behavioral adjustment. Conclusions:The APOE e4 allele was detrimental for long-term adaptive functioning in the context of positive parenting, whereas in less optimal parenting contexts, being a non-carrier was detrimental. We provide preliminary evidence for an interaction of APOE e4 status and parenting style in predicting long-term outcomes following early TBI. (JINS, 2016, 22, 859–864)

We investigated genetic and environmental correlations and gene by environment interactions (GxE) between depressive symptoms measured by the Beck Depression Inventory (BDI) and quantity smoked measured by number of cigarettes smoked per day (CPD) using quantitative genetic modeling. The population-based sample consisted of 12,063 twin individuals from the Finnish Twin Cohort Study. Bivariate Cholesky decomposition revealed that the phenotypic correlation (r = 0.09) between BDI and CPD was explained by shared genetic (r g = 0.18) and environmental (r e = 0.08) factors. GxE models incorporating moderator effects were built by using CPD as trait and BDI as moderator and vice versa. The importance of the genetic variance component increased with increasing moderator value in both models. Thus, the influence of genetic effects on variance of smoking quantity was enhanced in individuals with elevated depression score and vice versa; the genetic effects on depression variance were potentiated among heavy smokers. In conclusion, shared genetic and environmental factors as well as GxE underlie the association of smoking with depression.