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多基因与父母过度保护交互作用影响创造力的性别差异：一项基于全基因组关联分析的研究*
司思, 张舜, 苏妍, 张景焕
心理科学 ›› 2026, Vol. 49 ›› Issue (1) : 92-104.
PDF(1900 KB)
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多基因与父母过度保护交互作用影响创造力的性别差异：一项基于全基因组关联分析的研究*
Gender Differences in the Interaction between Polygenic Scores and Parental Overprotection on Creativity: A Genome-Wide Association Analysis
采用全基因组研究策略，对两个样本共1699名大学生的基因型和创造力进行检测，验证创造力的多基因性，检验多基因、父母过度保护与性别对创造力的交互作用，揭示特定性别的多基因-环境交互影响创造力的模式。结果发现（1）多基因分数对言语和图形创造力的直接预测作用均显著；（2）多基因分数能够调节母亲过度保护与言语创造力的关系，且该调节作用仅存在于男性个体中；（3）交互作用模式支持差别易感模型。这些发现有助于从多基因和环境交互作用的角度解释创造力性别差异的起源，为创造力累加的遗传可塑性提供了新的证据。
The debate about gender differences in creativity has never ceased, but conclusive evidence in favor of either gender has remained elusive. Nevertheless, in recent years, researchers have maintained a strong interest in revealing potential gender differences in creativity, and have attempted to find out the research for gender differences in creativity from the perspectives of “nature” and “nurture”, respectively. Currently, the use of molecular genetic techniques to identify genes associated with creativity and investigate their interactions with the environment (nurture) is a popular approach in creativity reserach. However, it is not known whether there is a gender-specific G×E effect (i.e., G×E×E effect) in the field of creativity. Parental overprotection is an important environmental factor affecting creativity, and its relationship with creativity may be influenced by plasticity genes. Studies have shown that this plasticity is not only affected by a single gene locus, but rather by multiple related genes acting together. Individual cumulative genetic plasticity may be the underlying cause of gender differences in mental development. Therefore, to investigate gender differences in creativity and to reveal the causes of gender differences in creativity, the present study is intended to adopt a genome-wide research strategy to investigate the mechanisms by which multiple genes (polygenic score, PGS) and parental overprotection (father and mother overprotection) interact to influence gender differences in creativity, from the perspective of the combined effects of “nature” and “nurture”.
The participants in this study were drawn from two samples. Sample 1 included 1,324 undergraduate students (Mage=18.56 years, 37.69% male) while sample 2 included 375 undergraduate students (Mage=18.80 years, 45.87% male). Both samples were of Han Chinese descent only and were free from reported neurological or psychiatric disorders. This study was approved by the Institutional Review Board of our university, and all participants provided informed consent to participate. Before genotyping, participants were required to undergo psychological testing. Subsequently, samples of their peripheral venous blood were collected for genotyping purposes. Participants’ creativity and parental overprotection were assessed using the Runco Creativity Assessment Battery (rCAB) and the Parental Bonding Instrument (PBI). Genotyping was conducted using the custom Illumina Infinium® Asian Screening Array (ASA-CHIA) and the Affymetrix Axiom® Genome-Wide CHB 1 and 2 arrays, respectively. Polygenic score (PGS) analysis was used to elucidate the effect of PGS on creativity. Then, multiple linear regression was conducted to test the three-way interaction among PGS, parental overprotection, and gender. To test the reliability of our results, approximately half of the samples were randomly selected and replicated 1,000 times using Bootstrap to conduct regression analyses for internal validation. Finally, the regions of significance (RoS) test was applied to explore whether gender-specific gene-environment interaction conformed to the differential susceptibility model.
The results revealed that the PGS constructed using the estimate derived from sample 1 significantly predicted verbal and figural creativity in sample 2. Besides, the three-way interaction between PGS, maternal overprotection, and gender on verbal creativity was significant. PGS was associated with verbal creativity when maternal overprotection of males was low, but PGS was not associated with verbal creativity when maternal overprotection of males was high. Finally, further examination of the gene-environment interaction model revealed that the PGS × maternal overprotection effect aligned with the differential susceptibility model. Specifically, males with a high PGS score were more susceptible to maternal overprotection. When maternal overprotection was low, these males tended to perform better; however, when it was high, their performance suffered. Accordingly, differences in cumulative genetic plasticity may be the main cause of gender differences in creativity.
Overall, these results provided a more precise explanation for the gender differences in creativity, not only emphasizing the need to examine the combined effects of genes associated with creativity but also highlighting the significance and value of integrating the use of multiple genes as well as important environmental indicators to reveal the mechanisms underlying the occurrence of creativity in individuals of different genders. In particular, given that the different “genetic plasticity” of individuals, personalized creativity intervention programs should be developed.
创造力 / 性别差异 / 全基因组研究 / 父母过度保护 / 多基因-环境交互作用
creativity / gender differences / genome-wide study / parental overprotection / polygenic score (PGS)-environment interaction
| [1] |
侯珂, 张云运, 骆方, 任萍. (2017). 邻里环境、父母监控和不良同伴交往对青少年问题行为的影响. 心理发展与教育, 33(1), 85-94.
|
| [2] |
单梦肖, 高岩, 李文福, 徐芳芳, 李功迎. (2019). 父母教养方式对创造性思维的影响: 性别的调节作用. 中国健康心理学杂志, 27(9), 1430-1435.
|
| [3] |
孙浩, 司思, 廖真真, 张景焕. (2022). TPH2基因rs4570625多态性和母亲权威教养对创造力的交互作用. 心理科学, 45(5), 1136-1143.
|
| [4] |
吴旻, 谢燕, 李妍. (2024). 母亲温暖和父亲温暖教养的一致性与农村儿童亲社会行为: 心理资本的中介作用. 心理与行为研究, 22(2), 251-257.
以588名4～5年级农村儿童为研究对象，采用多项式回归与响应面分析探讨母亲温暖和父亲温暖教养的一致性对农村儿童亲社会行为的影响，并考察心理资本在其中的作用。结果发现：(1)父母温暖教养一致时，父母温暖水平越高，农村儿童亲社会行为水平越高；(2)父母温暖教养不一致时，相较于父母温暖中等的儿童，高父亲温暖或高母亲温暖的儿童亲社会行为较高；(3)心理资本在父母温暖教养与农村儿童亲社会行为之间起部分中介作用。研究结果为农村儿童家庭教育及亲社会行为的干预提供新视角，对促进农村儿童积极适应具有重要的启示意义。
|
| [5] |
张景焕, 付萌萌, 辛于雯, 陈佩佩, 沙莎. (2020). 小学高年级学生创造力的发展: 性别差异及学校支持的作用. 心理学报, 52(9), 1057-1070.
对203名4年级学生进行3年追踪测试(到6年级), 采用多水平分析法考察创造力的发展趋势、性别差异以及教师/同伴支持对创造力发展的影响。结果表明：(1) 4~6年级小学生的流畅性呈线性增长趋势, 灵活性和独创性呈非线性增长趋势, 初始水平与增长速度呈正相关。(2)女生灵活性和独创性的初始水平高于男生。(3)教师支持正向预测男生灵活性的初始水平, 正向预测流畅性的初始水平和独创性的增长速度。(4)教师支持的发展正向预测流畅性的发展。
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| [6] |
In today's knowledge economy, creativity is more important than ever. But many companies unwittingly employ managerial practices that kill it. How? By crushing their employees' intrinsic motivation--the strong internal desire to do something based on interests and passions. Managers don't kill creativity on purpose. Yet in the pursuit of productivity, efficiency, and control--all worthy business imperatives--they undermine creativity. It doesn't have to be that way, says Teresa Amabile. Business imperatives can comfortably coexist with creativity. But managers will have to change their thinking first. Specifically, managers will need to understand that creativity has three parts: expertise, the ability to think flexibly and imaginatively, and motivation. Managers can influence the first two, but doing so is costly and slow. It would be far more effective to increase employees' intrinsic motivation. To that end, managers have five levers to pull: the amount of challenge they give employees, the degree of freedom they grant around process, the way they design work groups, the level of encouragement they give, and the nature of organizational support. Take challenge as an example. Intrinsic motivation is high when employees feel challenged but not overwhelmed by their work. The task for managers, therefore, becomes matching people to the right assignments. Consider also freedom. Intrinsic motivation--and thus creativity--soars when managers let people decide how to achieve goals, not what goals to achieve. Managers can make a difference when it comes to employee creativity. The result can be truly innovative companies in which creativity doesn't just survive but actually thrives.
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| [7] |
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| [8] |
Evolutionary-biological reasoning suggests that individuals should be differentially susceptible to environmental influences, with some people being not just more vulnerable than others to the negative effects of adversity, as the prevailing diathesis-stress view of psychopathology (and of many environmental influences) maintains, but also disproportionately susceptible to the beneficial effects of supportive and enriching experiences (or just the absence of adversity). Evidence consistent with the proposition that individuals differ in plasticity is reviewed. The authors document multiple instances in which (a) phenotypic temperamental characteristics, (b) endophenotypic attributes, and (c) specific genes function less like "vulnerability factors" and more like "plasticity factors," thereby rendering some individuals more malleable or susceptible than others to both negative and positive environmental influences. Discussion focuses upon limits of the evidence, statistical criteria for distinguishing differential susceptibility from diathesis stress, potential mechanisms of influence, and unknowns in the differential-susceptibility equation.
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| [9] |
Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.
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| [10] |
A polygenic score (PGS) or polygenic risk score (PRS) is an estimate of an individual's genetic liability to a trait or disease, calculated according to their genotype profile and relevant genome-wide association study (GWAS) data. While present PRSs typically explain only a small fraction of trait variance, their correlation with the single largest contributor to phenotypic variation-genetic liability-has led to the routine application of PRSs across biomedical research. Among a range of applications, PRSs are exploited to assess shared etiology between phenotypes, to evaluate the clinical utility of genetic data for complex disease and as part of experimental studies in which, for example, experiments are performed that compare outcomes (e.g., gene expression and cellular response to treatment) between individuals with low and high PRS values. As GWAS sample sizes increase and PRSs become more powerful, PRSs are set to play a key role in research and stratified medicine. However, despite the importance and growing application of PRSs, there are limited guidelines for performing PRS analyses, which can lead to inconsistency between studies and misinterpretation of results. Here, we provide detailed guidelines for performing and interpreting PRS analyses. We outline standard quality control steps, discuss different methods for the calculation of PRSs, provide an introductory online tutorial, highlight common misconceptions relating to PRS results, offer recommendations for best practice and discuss future challenges.
|
| [11] |
|
| [12] |
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
Divergent thinking (DT) has attracted research interest because of its potential role in early diagnosis and rehabilitation programs for patients affected by neurodegenerative diseases. Recently, DT has received even more attention because of its proven relationship with cognitive reserve (CR) and the possibility of a standardized assessment. However, few studies have investigated this ability in dementia patients, and even less is known about patients affected by Mild Cognitive Impairment (MCI). Thus, this study aims to investigate DT abilities in MCI patients.A total of 25 MCI patients and 25 healthy controls subjects (HC; from a random selection of 50) matched for age, gender, and educational level were enrolled. General cognitive functioning was measured by the Montreal Cognitive Assessment (MoCA), while the Abbreviated Torrance Test for Adults (ATTA) was selected to measure DT.MANOVA analysis did not reveal any significant differences in DT abilities between MCI patients and HC except for the figural indicator score. A logistic hierarchical regression analysis revealed that the figural indicator score added an 8% of accuracy in the prediction of the group variable over the general cognition measure (MoCA).MCI patients seem to perform significantly worse than HC only in the figural DT score and this evidence has significant practical implications. First, that figural DT seemed to decrease even earlier than verbal DT and could therefore be taken into account for early diagnosis of MCI patients. On the contrary, the sparing of all the other DT skills (such as verbal DT skills, fluency, flexibility, originality, and elaboration) may suggest that, given its relationship with CR, verbal DT could instead be considered a possible target for prevention or early cognitive stimulation interventions.Copyright © 2020 Fusi, Ferrari, Zanetti, Crepaldi, Bersanini, Paladino, Colautti, Rozzini, Antonietti and Rusconi.
|
| [20] |
|
| [21] |
|
| [22] |
This meta-analysis of 161 published and unpublished manuscripts was conducted to determine whether the association between parenting and delinquency exists and what the magnitude of this linkage is. The strongest links were found for parental monitoring, psychological control, and negative aspects of support such as rejection and hostility, accounting for up to 11% of the variance in delinquency. Several effect sizes were moderated by parent and child gender, child age, informant on parenting, and delinquency type, indicating that some parenting behaviors are more important for particular contexts or subsamples. Although both dimensions of warmth and support seem to be important, surprisingly very few studies focused on parenting styles. Furthermore, fewer than 20% of the studies focused on parenting behavior of fathers, despite the fact that the effect of poor support by fathers was larger than poor maternal support, particularly for sons. Implications for theory and parenting are discussed.
|
| [23] |
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| [24] |
People may experience an "oho" moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-O-methyltransferase (COMT) gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving.
|
| [25] |
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| [26] |
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| [27] |
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| [28] |
The goal of this study was to examine how the parenting dimensions of both mothers and fathers independently and together predict adolescent outcomes in three domains: sympathy, self-worth, and social competence. One-hundred eight adolescents completed self-report measures on their perceived relationship with parents, sympathy, social competence, and self-worth. Perceived maternal supportandrigid control were the most consistent predictors of adolescent adjustment. High levels of perceived maternal support and low levels of maternal rigid control were related to adolescents’reports of sympathy, social competence, and self-worth. In contrast, support and control from fathers was generally unrelated to adolescent adjustment. The one exception was in predicting sympathy, where father support interacted with maternal support in predicting sympathy. When perceived support from fathers was high, maternal support was unrelated to sympathy. In contrast, when perceived supportfrom fathers was low, perceived maternal support was a statistically significant predictor of sympathy.
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| [29] |
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| [30] |
Multiple sclerosis (MS) is an autoimmune disorder influenced by genetic and environmental factors. Many studies have provided insights into genetic factors’ contribution to MS via large-scale genome-wide association study (GWAS) datasets. However, genetic variants identified to date do not adequately explain genetic risks for MS. This study hypothesized that novel MS risk genes could be identified by analyzing the MS-GWAS dataset using gene-based tests. We analyzed a GWAS dataset consisting of 9,772 MS cases and 17,376 healthy controls of European descent. We performed gene-based tests of 464,357 autosomal single nucleotide polymorphisms (SNPs) using two methods (PLINK and VEGAS2) and identified 28 shared genes satisfied p-value < 4.56 × 10–6. In further gene expression analysis, ten of the 28 genes were significantly differentially expressed in the MS case-control gene expression omnibus (GEO) database. GALC and HLA-DOB showed the most prominent differences in gene expression (two- and three-fold, respectively) between MS patients and healthy controls. In conclusion, our results reveal more information about MS hereditary characteristics and provide a basis for further studies.
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| [31] |
Creativity represents one of the most important and partially heritable human characteristics, yet little is known about its genetic basis. Epidemiological studies reveal associations between creativity and psychiatric disorders as well as multiple personality and behavioral traits. To test whether creativity and these disorders or traits share genetic basis, we performed genome-wide association studies (GWAS) followed by polygenic risk score (PRS) analyses. Two cohorts of Han Chinese subjects (4,834 individuals in total) aged 18-45 were recruited for creativity measurement using typical performance test. After exclusion of the outliers with significantly deviated creativity scores and low-quality genotyping results, 4,664 participants were proceeded for GWAS. We conducted PRS analyses using both the classical pruning and thresholding (P+T) method and the LDpred method. The extent of polygenic risk was estimated through linear regression adjusting for the top 3 genotyping principal components. R2 was used as a measurement of the explained variance. PRS analyses demonstrated significantly positive genetic overlap, respectively, between creativity with schizophrenia ((P+T) method: R2(max) ~.196%, P =.00245; LDpred method: R2(max) ~.226%, P =.00114), depression ((P+T) method: R2(max) ~.178%, P =.00389; LDpred method: R2(max) ~.093%, P =.03675), general risk tolerance ((P+T) method: R2(max) ~.177%, P =.00399; LDpred method: R2(max) ~.305%, P =.00016), and risky behaviors ((P+T) method: R2(max) ~.187%, P =.00307; LDpred method: R2(max) ~.155%, P =.00715). Our results suggest that human creativity is probably a polygenic trait affected by numerous variations with tiny effects. Genetic variations that predispose to psychiatric disorders and risky behaviors may underlie part of the genetic basis of creativity, confirming the epidemiological associations between creativity and these traits.© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.
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| [32] |
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| [33] |
Creative thinking plays a vital role in almost all aspects of human life. However, little is known about the neural and genetic mechanisms underlying creative thinking. Based on a cross-validation based predictive framework, we searched from the whole-brain connectome (34,716 functional connectivities) and whole genome data (309,996 SNPs) in two datasets (all collected by Southwest University, Chongqing) consisting of altogether 236 subjects, for a better understanding of the brain and genetic underpinning of creativity. Using the Torrance Tests of Creative Thinking score, we found that high figural creativity is mainly related to high functional connectivity between the executive control, attention, and memory retrieval networks (strong top-down effects); and to low functional connectivity between the default mode network, the ventral attention network, and the subcortical and primary sensory networks (weak bottom-up processing) in the first dataset (consisting of 138 subjects). High creativity also correlates significantly with mutations of genes coding for both excitatory and inhibitory neurotransmitters. Combining the brain connectome and the genomic data we can predict individuals' creativity scores with an accuracy of 78.4%, which is significantly better than prediction using single modality data (gene or functional connectivity), indicating the importance of combining multi-modality data. Our neuroimaging prediction model built upon the first dataset was cross-validated by a completely new dataset of 98 subjects (r = 0.267, p = 0.0078) with an accuracy of 64.6%. In addition, the creativity-related functional connectivity network we identified in the first dataset was still significantly correlated with the creativity score in the new dataset (p<10). In summary, our research demonstrates that strong top-down control versus weak bottom-up processes underlie creativity, which is modulated by competition between the glutamate and GABA neurotransmitter systems. Our work provides the first insights into both the neural and the genetic bases of creativity.Copyright © 2018 Elsevier Inc. All rights reserved.
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| [34] |
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| [35] |
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| [36] |
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| [37] |
Advances in the conceptualization and measurement of life stress in the past 2 decades raise several questions concerning traditional diathesis-stress theories of psychopathology. First, comprehensive measures of life stress force investigators to become more precise about the particular stressful circumstances hypothesized to interact with diatheses. Second, the influence of the diathesis on a person's life is typically ignored, which results in several types of possible bias in the assessment of life stress. Finally, information is available on diatheses and stress for specific disorders to provide a foundation for more empirically based hypotheses about diathesis-stress interactions. This possibility is outlined for depression. Such an approach provides the basis for developing broader, yet more specific, frameworks for investigating diathesis-stress theories of psychopathology in general and of depression in particular.
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| [38] |
In the field of physiological study of human intelligence, strong evidence of a more efficient operation (i.e., less activation) of the brain in brighter individuals (the neural efficiency hypothesis) can be found. Most studies in this field have used single, homogeneous tasks and have not examined sex differences. In analyzing the extent of Event-related Desynchronization (ERD) in the EEG during the performance of a verbal and a visuo-spatial task, we recently found that males and females display neural efficiency primarily in the domain where they usually perform better (i.e., verbal in females and spatial in males; cf. A.C. Neubauer, A. Fink, D.G. Schrausser, Intelligence and neural efficiency: the influence of task content and sex on brain-IQ relationship. Intelligence, 30 (2002) 515-536). However, this interpretation was complicated by differences in the complexity of the two tasks. By using a verbal (semantic) and a spatial (rotation) task of comparable complexity in this research, we sought to replicate and extend our earlier findings by additionally considering the individual differences in intelligence structure and the topographical distribution over the cortex. Findings were similar to the previous study: Females (n = 35) display neural efficiency (i.e., less brain activation in brighter individuals) primarily during the verbal task, males (n = 31) in the spatial task. However, the strength of this brain activation-IQ relationship varies with the intelligence factor: In males, the highest correlations were observed for spatial IQ, in females for verbal IQ. Furthermore, the sexes displayed topographical differences of neural efficiency patterns.
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| [39] |
Sexual dimorphism in anatomical, physiological and behavioural traits are characteristics of many vertebrate species. In humans, sexual dimorphism is also observed in the prevalence, course and severity of many common diseases, including cardiovascular diseases, autoimmune diseases and asthma. Although sex differences in the endocrine and immune systems probably contribute to these observations, recent studies suggest that sex-specific genetic architecture also influences human phenotypes, including reproductive, physiological and disease traits. It is likely that an underlying mechanism is differential gene regulation in males and females, particularly in sex steroid-responsive genes. Genetic studies that ignore sex-specific effects in their design and interpretation could fail to identify a significant proportion of the genes that contribute to risk for complex diseases.
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| [40] |
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| [41] |
Gender-moderated gene-environment interactions are rarely explored, raising concerns about inaccurate specification of etiological models and inferential errors. The current study examined the influence of gender, negative and positive daily life events, and GABRA2 genotype (SNP rs279871) on alcohol dependence, testing two- and three-way interactions between these variables using multi-level regression models fit to data from 2,281 White participants in the Collaborative Study on the Genetics of Alcoholism. Significant direct effects of variables of interest were identified, as well as gender-specific moderation of genetic risk on this SNP by social experiences. Higher levels of positive life events were protective for men with the high-risk genotype, but not among men with the low-risk genotype or women, regardless of genotype. Our findings support the disinhibition theory of alcohol dependence, suggesting that gender differences in social norms, constraints and opportunities, and behavioral undercontrol may explain men and women's distinct patterns of association.
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| [42] |
Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.
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| [43] |
The adducin family of proteins interacts with the actin cytoskeleton and the plasma membrane in a calcium- and cAMP-dependent manner. Thus, adducins may be involved in changes in cytoskeletal organization resulting from synaptic stimulation. beta-Adducin knock-out mice were examined in physiological and behavioral paradigms related to synaptic plasticity to elucidate the role the adducin family plays in processes underlying learning and memory. In situ hybridization for alpha- and beta-adducin demonstrates that these mRNAs are found throughout the brain, with high levels of expression in the hippocampus. Schaffer collateral-CA1 tetanic long-term potentiation decayed rapidly in acute hippocampal slices from beta-adducin knock-out mice, although baseline spine morphology and postsynaptic density were normal. Interestingly, the input-output relationship was significantly increased in hippocampal slices from beta-adducin knock-out mice. Furthermore, beta-adducin knock-out mice were impaired in performance of fear conditioning and the water maze paradigm. The current results indicate that beta-adducin may play an important role in the cellular mechanisms underlying activity-dependent synaptic plasticity associated with learning and memory.
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| [44] |
A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R (2) ≈ 0.02%), reached genome-wide significance (p < 5 × 10(-8)) in a large discovery sample and were replicated in an independent sample (p <.05). The study also reported associations between educational attainment and indices of SNPs called "polygenic scores." In three studies, we evaluated the robustness of these findings. Study 1 showed that the associations with all three SNPs were replicated in another large (N = 34,428) independent sample. We also found that the scores remained predictive (R (2) ≈ 2%) in regressions with stringent controls for stratification (Study 2) and in new within-family analyses (Study 3). Our results show that large and therefore well-powered genome-wide-association studies can identify replicable genetic associations with behavioral traits. The small effect sizes of individual SNPs are likely to be a major contributing factor explaining the striking contrast between our results and the disappointing replication record of most candidate-gene studies. © The Author(s) 2014.
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| [45] |
This report describes the state of the art in distinguishing data generated by differential susceptibility from diathesis-stress models. We discuss several limitations of existing practices for probing interaction effects and offer solutions that are designed to better differentiate differential susceptibility from diathesis-stress models and quantify their corresponding implications. In addition, we demonstrate the utility of these methods by revisiting published evidence suggesting that temperamental difficulty serves as a marker of enhanced susceptibility to early maternal caregiving across a range of outcome domains in the NICHD Study of Early Child Care and Youth Development. We find that, with the exception of mother reports of psychopathology, there is consistent evidence in the Study of Early Child Care and Youth Development that the predictive significance of early sensitivity is moderated by difficult temperament over time. However, differential susceptibility effects emerged primarily for teacher reports of academic skills, social competence, and symptomatology. In contrast, effects more consistent with the diathesis-stress model were obtained for mother reports of social skills and objective tests of academic skills. We conclude by discussing the value of the application of this work to the next wave of Gene × Environment studies focused on early caregiving experiences.
|
| [46] |
|
| [47] |
|
| [48] |
|
| [49] |
|
| [50] |
|
| [51] |
|
| [52] |
|
| [53] |
|
| [54] |
|
| [55] |
|
| [56] |
|
| [57] |
|
| [58] |
|
| [59] |
|
| [60] |
|
| [61] |
|
| [62] |
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