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Statistical and Machine Learning Analysis in Brain-Imaging Genetics: A Review of Methods. 脑成像遗传学中的统计和机器学习分析:方法综述》。
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-01 Epub Date: 2024-02-10 DOI: 10.1007/s10519-024-10177-y
Connor L Cheek, Peggy Lindner, Elena L Grigorenko

Brain-imaging-genetic analysis is an emerging field of research that aims at aggregating data from neuroimaging modalities, which characterize brain structure or function, and genetic data, which capture the structure and function of the genome, to explain or predict normal (or abnormal) brain performance. Brain-imaging-genetic studies offer great potential for understanding complex brain-related diseases/disorders of genetic etiology. Still, a combined brain-wide genome-wide analysis is difficult to perform as typical datasets fuse multiple modalities, each with high dimensionality, unique correlational landscapes, and often low statistical signal-to-noise ratios. In this review, we outline the progress in brain-imaging-genetic methodologies starting from early massive univariate to current deep learning approaches, highlighting each approach's strengths and weaknesses and elongating it with the field's development. We conclude by discussing selected remaining challenges and prospects for the field.

脑成像-遗传分析是一个新兴的研究领域,旨在将描述大脑结构或功能的神经成像模式数据与捕捉基因组结构和功能的遗传数据进行整合,以解释或预测大脑的正常(或异常)表现。脑成像-基因研究为了解复杂的脑相关疾病/遗传病因紊乱提供了巨大的潜力。然而,由于典型的数据集融合了多种模式,每种模式都具有高维度、独特的相关性景观,而且统计信噪比通常较低,因此很难进行全脑基因组的综合分析。在这篇综述中,我们概述了大脑成像遗传学方法的进展,从早期的大规模单变量方法到目前的深度学习方法,强调了每种方法的优缺点,并随着该领域的发展而不断延伸。最后,我们讨论了该领域面临的挑战和前景。
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引用次数: 0
Are Genetic and Environmental Risk Factors for Psychopathology Amplified in Children with Below-Average Intelligence? A Population-Based Twin Study. 智力低于平均水平的儿童的精神病理学遗传和环境风险因素是否会放大?一项基于人口的双胞胎研究。
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-01 Epub Date: 2024-02-14 DOI: 10.1007/s10519-023-10174-7
Susanne Bruins, Elsje van Bergen, Maurits W Masselink, Stefania A Barzeva, Catharina A Hartman, Roy Otten, Nanda N J Rommelse, Conor V Dolan, Dorret I Boomsma

There is a negative association between intelligence and psychopathology. We analyzed data on intelligence and psychopathology to assess this association in seven-year-old Dutch twin pairs (ranging from 616 to 14,150 depending on the phenotype) and estimated the degree to which genetic and environmental factors common to intelligence and psychopathology explain the association. Secondly, we examined whether genetic and environmental effects on psychopathology are moderated by intelligence. We found that intelligence, as assessed by psychometric IQ tests, correlated negatively with childhood psychopathology, as assessed by the DSM-oriented scales of the Child Behavior Check List (CBCL). The correlations ranged between - .09 and - .15 and were mainly explained by common genetic factors. Intelligence moderated genetic and environmental effects on anxiety and negative affect, but not those on ADHD, ODD, and autism. The heritability of anxiety and negative affect was greatest in individuals with below-average intelligence. We discuss mechanisms through which this effect could arise, and we end with some recommendations for future research.

智力与精神病理学之间存在负相关。我们分析了有关智力和精神病理学的数据,以评估7岁荷兰双胞胎(根据表型,从616对到14150对不等)的这种关联,并估计了智力和精神病理学共同的遗传和环境因素对这种关联的解释程度。其次,我们研究了遗传和环境对精神病理学的影响是否会受到智力的调节。我们发现,通过心理智商测试评估的智力与通过儿童行为检查表(CBCL)中以 DSM 为导向的量表评估的儿童精神病理学呈负相关。相关性介于-.09和-.15之间,主要由共同的遗传因素解释。智力可以调节遗传和环境对焦虑和负面情绪的影响,但不能调节对多动症、定向障碍和自闭症的影响。智力低于平均水平的个体焦虑和消极情绪的遗传率最高。我们讨论了这种效应可能产生的机制,最后对未来的研究提出了一些建议。
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引用次数: 0
A Genetically Informed Study of the Association Between Perceived Stress and Loneliness. 关于感知到的压力与孤独之间关系的基因信息研究。
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-01 Epub Date: 2024-02-11 DOI: 10.1007/s10519-023-10176-5
Ryan Moshtael, Morgan E Lynch, Glen E Duncan, Christopher R Beam

Although research shows a strong positive association between perceived stress and loneliness, the genetic and environmental etiology underlying their association remains unknown. People with a genetic predisposition to perceived stress, for example, may be more prone to feeling lonely and vice versa. Conversely, unique factors in people's lives may explain differences in perceived stress levels that, in turn, affect feelings of loneliness. We tested whether genetic factors, environmental factors, or both account for the association between perceived stress and loneliness. Participants were 3,066 individual twins (nFemale = 2,154, 70.3%) from the Washington State Twin Registry who completed a survey during April-May, 2020. Structural equation modeling was used to analyze the item-level perceived stress and loneliness measures. The correlation between latent perceived stress and latent loneliness was .68. Genetic and nonshared environmental variance components underlying perceived stress accounted for 3.71% and 23.26% of the total variance in loneliness, respectively. The genetic correlation between loneliness and perceived stress was .45 and did not differ significantly between men and women. The nonshared environmental correlation was .54 and also did not differ between men and women. Findings suggest that holding constant the strong genetic association between perceived stress and loneliness, unique life experiences underlying people's perceived stress account for individual differences in loneliness.

尽管研究表明,感知到的压力和孤独感之间存在着很强的正相关性,但二者之间的遗传和环境病因仍然不得而知。例如,具有感知压力遗传倾向的人可能更容易感到孤独,反之亦然。反之,人们生活中的独特因素可能会解释人们感知到的压力水平的差异,进而影响孤独感。我们测试了遗传因素、环境因素或两者是否能解释感知压力与孤独感之间的关联。参与者是华盛顿州双胞胎登记处的 3066 对双胞胎(nFemale = 2,154, 70.3%),他们在 2020 年 4-5 月间完成了一项调查。结构方程模型用于分析项目层面的感知压力和孤独感测量。潜在感知压力和潜在孤独感之间的相关性为 0.68。感知压力的遗传和非共享环境变异成分分别占孤独感总变异的 3.71% 和 23.26%。孤独感与感知压力之间的遗传相关性为 0.45,男女之间差异不大。非共享环境相关性为 0.54,男女之间也没有差异。研究结果表明,在感知到的压力与孤独感之间的遗传相关性保持不变的情况下,人们感知到的压力背后的独特生活经历是造成孤独感个体差异的原因。
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引用次数: 0
Altered Grooming Cycles in Transgenic Drosophila. 转基因果蝇新陈代谢周期的改变
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-01 Epub Date: 2024-03-27 DOI: 10.1007/s10519-024-10180-3
John M Ringo, Daniel Segal

Head grooming in Drosophila consists of repeated sweeps of the legs across the head, comprising regular cycles. We used the GAL4-UAS system to study the effects of overexpressing shibirets1 and of Adar knockdown via RNA interference, on the period of head-grooming cycles in Drosophila. Overexpressing shibirets1 interferes with synaptic vesicle recycling and thus with cell communication, while Adar knockdown reduces RNA editing of neuronal transcripts for a large number of genes. All transgenic flies and their controls were tested at 22° to avoid temperature effects; in wild type, cycle frequency varied with temperature with a Q10 of 1.3. Two experiments were performed with transgenic shibirets1: (1) each fly was heat-shocked for 10 min at 30° immediately before testing at 22° and (2) flies were not heat shocked. In both experiments, cycle period was increased when shibirets1 was overexpressed in all neurons, but was not increased when shibirets1 was overexpressed in motoneurons alone. We hypothesize that grooming cycles in flies overexpressing shibirets1 are lengthened because of synaptic impairment in neural circuits that control head-grooming cycles. In flies with constitutive, pan-neuronal Adar knockdown, cycle period was more variable within individuals, but mean cycle period was not significantly altered. We conclude that RNA editing is essential for the maintenance of within-individual stereotypy of head-grooming cycles.

果蝇的头部梳理包括腿部反复扫过头部,形成有规律的周期。我们利用 GAL4-UAS 系统研究了过表达 shibirets1 和通过 RNA 干扰敲除 Adar 对果蝇头部梳理周期的影响。过表达shibirets1会干扰突触小泡的再循环,从而影响细胞通讯,而敲除Adar会减少神经元转录本中大量基因的RNA编辑。为避免温度影响,所有转基因苍蝇及其对照组都在 22° 进行了测试;野生型的周期频率随温度变化,Q10 为 1.3。对转基因 shibirets1 进行了两次实验:(1) 每只苍蝇在 22°下测试前立即在 30°下热休克 10 分钟;(2) 不对苍蝇进行热休克。在这两项实验中,当 shibirets1 在所有神经元中过表达时,梳理周期会延长,但当 shibirets1 仅在运动神经元中过表达时,周期不会延长。我们推测,过表达 shibirets1 的苍蝇的梳理周期延长是因为控制头部梳理周期的神经回路的突触受损。在构成性、泛神经元 Adar 敲除的苍蝇中,个体间的周期变化更大,但平均周期没有显著变化。我们的结论是,RNA编辑对维持个体内头部梳理周期的刻板性至关重要。
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引用次数: 0
Peter Driscoll (1938-2024): A Generous, Honest and Humble Man in Science. 彼得-德里斯科(1938-2024 年):科学界慷慨、诚实和谦逊的人
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-25 DOI: 10.1007/s10519-024-10181-2
A. Fernández-Teruel
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引用次数: 0
The Detection of Environmental Influences on Academic Achievement Appears to Depend on the Analytic Approach 环境对学习成绩影响的检测似乎取决于分析方法
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-04-08 DOI: 10.1007/s10519-024-10179-w
S. Alexandra Burt, Patrick O’Keefe, Wendy Johnson, Daniel Thaler, Leslie D. Leve, Misaki N. Natsuaki, David Reiss, Daniel S. Shaw, Jody M. Ganiban, Jenae M. Neiderhiser

One long-standing analytic approach in adoption studies is to examine correlations between features of adoptive homes and outcomes of adopted children (hereafter termed ‘measured environment correlations’) to illuminate environmental influences on those associations. Although results from such studies have almost uniformly suggested modest environmental influences on adopted children’s academic achievement, other work has indicated that adopted children’s achievement is routinely higher than that of their reared-apart family members, often substantially so. We sought to understand this discrepancy. We examined academic achievement and literacy-promotive features of the home in 424 yoked adoptive/biological families participating in the Early Growth and Development Study (EGDS; i.e., adopted children, adoptive mothers, birth mothers, and biological siblings of the adopted children remaining in the birth homes) using an exhaustive modeling approach. Results indicated that, as anticipated, adopted children scored up to a full standard deviation higher on standardized achievement tests relative to their birth mothers and reared-apart biological siblings. Moreover, these achievement differences were associated with differences in the literacy-promotive features of the adoptive and birth family homes, despite minimal measured environment correlations within adoptive families. A subsequent simulation study highlighted noise in measured environmental variables as an explanation for the decreased utility of measured environment correlations. We conclude that the field’s heavy focus on measured environment correlations within adoptive families may have obscured detection of specific environmental effects on youth outcomes, and that future adoption studies should supplement their measured environment analyses with mean differences between reared-apart relatives.

长期以来,收养研究中的一种分析方法是研究收养家庭的特征与被收养儿童成绩之间的相关性(以下称为 "测量环境相关性"),以阐明环境对这些相关性的影响。尽管此类研究的结果几乎一致地表明,环境对被收养儿童的学业成绩影响不大,但其他研究却表明,被收养儿童的成绩通常高于与其分开的家庭成员的成绩,而且往往高出很多。我们试图了解这种差异。我们采用一种详尽的建模方法,研究了 424 个参与早期成长与发展研究(EGDS,即被收养儿童、收养母亲、亲生母亲以及被收养儿童留在亲生家庭的亲生兄弟姐妹)的寄养/亲生家庭的学业成绩和促进识字的家庭特征。结果表明,正如预期的那样,被收养儿童在标准化成绩测试中的得分要比他们的生母和与他们分开的亲生兄弟姐妹高出整整一个标准差。此外,这些成绩差异还与收养家庭和亲生家庭在促进识字方面的差异有关,尽管收养家庭内部的测量环境相关性很小。随后的一项模拟研究强调,测量环境变量中的噪音是测量环境相关性效用降低的一个原因。我们的结论是,该领域对收养家庭内部测量环境相关性的高度关注,可能会掩盖对青少年结果的特定环境影响的检测,未来的收养研究应该用重新分开的亲属之间的平均差异来补充测量环境分析。
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引用次数: 0
Peter McGuffin CBE (February 4, 1949–January 30, 2024) 彼得-麦克格芬 CBE(1949 年 2 月 4 日-2024 年 1 月 30 日)
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-03-19 DOI: 10.1007/s10519-024-10178-x
Anita Thapar
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引用次数: 0
Interactions Between Genetic, Prenatal Substance Use, Puberty, and Parenting are Less Important for Understanding Adolescents' Internalizing, Externalizing, and Substance Use than Developmental Cascades in Multifactorial Models. 在多因素模型中,遗传、产前物质使用、青春期和父母关系之间的相互作用对于理解青少年的内在化、外在化和物质使用不如发育级联重要。
IF 2.6 4区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-03-01 Epub Date: 2023-10-15 DOI: 10.1007/s10519-023-10164-9
Kristine Marceau, Amy M Loviska, Gregor Horvath, Valerie S Knopik

This study tested interactions among puberty-related genetic risk, prenatal substance use, harsh discipline, and pubertal timing for the severity and directionality (i.e., differentiation) of externalizing and internalizing problems and adolescent substance use. This is a companion paper to Marceau et al. (2021) which examined the same influences in developmental cascade models. Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 4504 White boys, n = 4287 White girls assessed from the prenatal period through 18.5 years). We hypothesized generally that later predictors would strengthen the influence of puberty-related genetic risk, prenatal substance use exposure, and pubertal risk on psychopathology and substance use (two-way interactions), and that later predictors would strengthen the interactions of earlier influences on psychopathology and substance use (three-way interactions). Interactions were sparse. Although all fourteen interactions showed that later influences can exacerbate or trigger the effects of earlier ones, they often were not in the expected direction. The most robust moderator was parental discipline, and differing and synergistic effects of biological and socially-relevant aspects of puberty were found. In all, the influences examined here operate more robustly in developmental cascades than in interaction with each other for the development of psychopathology and transitions to substance use.

这项研究测试了与青春期相关的遗传风险、产前药物使用、严厉的纪律和青春期时间之间的相互作用,以了解外化和内化问题以及青少年药物使用的严重性和方向性(即分化)。这是Marceau等人的配套论文。(2021)研究了发展级联模型中的相同影响。数据来自雅芳父母和儿童纵向研究(ALSPAC)队列(n = 4504名白人男孩,n = 4287名白人女孩从产前到18.5年接受评估)。我们普遍假设,后期预测因子会加强青春期相关遗传风险、产前物质使用暴露和青春期风险对精神病理学和物质使用的影响(双向相互作用),而后期预测因子则会加强早期影响对精神病理学和物质使用的相互作用(三方相互作用)。相互作用很少。尽管所有14种相互作用都表明,后期的影响会加剧或触发早期的影响,但它们往往没有朝着预期的方向发展。最有力的调节因素是父母的管教,青春期的生物学和社会相关方面存在不同的协同效应。总之,在精神病理学的发展和向物质使用的过渡过程中,本文研究的影响在发育级联中比在相互作用中更为强烈。
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引用次数: 0
Genotype-Environment Interaction in ADHD: Genetic Predisposition Determines the Extent to Which Environmental Influences Explain Variability in the Symptom Dimensions Hyperactivity and Inattention. 多动症的基因型与环境相互作用:遗传易感性决定了环境影响在多动和注意力不集中症状维度上的可解释程度。
IF 2.6 4区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-03-01 Epub Date: 2024-01-25 DOI: 10.1007/s10519-023-10168-5
Inga Schwabe, Miljan Jović, Kaili Rimfeld, Andrea G Allegrini, Stéphanie M van den Berg

Although earlier research has shown that individual differences on the spectrum of attention deficit hyperactivity disorder (ADHD) are highly heritable, emerging evidence suggests that symptoms are associated with complex interactions between genes and environmental influences. This study investigated whether a genetic predisposition [Note that the term 'genetic predisposition' was used in this manuscript to refer to an estimate based on twin modeling (an individual's score on the latent trait that resembles additive genetic influences) in the particular population being examined.] for the symptom dimensions hyperactivity and inattention determines the extent to which unique-environmental influences explain variability in these symptoms. To this purpose, we analysed a sample drawn from the Twins Early Development Study (TEDS) that consisted of item-level scores of 2168 16-year-old twin pairs who completed both the Strengths and Difficulties Questionnaire (SDQ; Goodman, in J Child Psychol Psychiatry 38:581-586, 1997) and the Strength and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN; Swanson, in Paper presented at the meeting of the American Psychological Association, Los Angeles, 1981) questionnaire. To maximize the psychometric information to measure ADHD symptoms, psychometric analyses were performed to investigate whether the items from the two questionnaires could be combined to form two longer subscales. In the estimation of genotype-environment interaction, we corrected for error variance heterogeneity in the measurement of ADHD symptoms through the application of item response theory (IRT) measurement models. A positive interaction was found for both hyperactivity (e.g., [Formula: see text] = 2.20 with 95% highest posterior density interval equal to [1.79;2.65] and effect size equal to 3.00) and inattention (e.g., [Formula: see text] = 2.16 with 95% highest posterior density interval equal to [1.56;2.79] and effect size equal to 3.07). These results indicate that unique-environmental influences were more important in creating individual differences in both hyperactivity and inattention for twins with a genetic predisposition for these symptoms than for twins without such a predisposition.

尽管早期研究表明,注意力缺陷多动障碍(ADHD)的个体差异具有高度遗传性,但新出现的证据表明,症状与基因和环境影响之间复杂的相互作用有关。本研究调查了多动和注意力不集中这两个症状维度的遗传易感性[请注意,本手稿中使用的 "遗传易感性 "一词是指根据双胞胎建模得出的估计值(个体在潜在特质上的得分类似于遗传影响的加法)。为此,我们分析了从双胞胎早期发展研究(TEDS)中抽取的样本,该样本包括 2168 对 16 岁双胞胎的项目级得分,他们同时填写了优势与困难问卷(SDQ;Goodman,发表于《儿童心理学精神病学》38:581-586,1997 年)和多动症症状与正常行为的优势与劣势问卷(SWAN;Swanson,发表于 1981 年洛杉矶美国心理学会会议论文)。为了最大限度地利用心理测量信息来测量多动症症状,我们进行了心理测量分析,以研究是否可以将两份问卷中的项目合并成两个较长的分量表。在估计基因型与环境的交互作用时,我们通过应用项目反应理论(IRT)测量模型来校正多动症症状测量中的误差方差异质性。结果发现,多动(例如,[计算公式:见正文] = 2.20,95%最高后验密度区间为[1.79;2.65],效应大小为3.00)和注意力不集中(例如,[计算公式:见正文] = 2.16,95%最高后验密度区间为[1.56;2.79],效应大小为3.07)均存在正交互作用。这些结果表明,与无遗传倾向的双胞胎相比,有遗传倾向的双胞胎在多动和注意力不集中方面的个体差异更重要的是受独特环境的影响。
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引用次数: 0
Key Grazing Behaviours of Beef Cattle Identify Specific Genotypes of the Glutamate Metabotropic Receptor 5 Gene (GRM5). 肉牛的主要放牧行为确定了谷氨酸代谢受体 5 基因 (GRM5) 的特定基因型。
IF 2.6 4区 医学 Q1 Agricultural and Biological Sciences Pub Date : 2024-03-01 Epub Date: 2024-01-16 DOI: 10.1007/s10519-023-10169-4
Cristian Anibal Moreno García, Susana Beatríz Perelman, Robyn Dynes, Thomas M R Maxwell, Huitong Zhou, Jonathan Hickford

Genotype-phenotype associations between the bovine genome and grazing behaviours measured over time and across contexts have been reported in the past decade, with these suggesting the potential for genetic control over grazing personalities in beef cattle. From the large array of metrics used to describe grazing personality behaviours (GP-behaviours), it is still unclear which ones are linked to specific genes. Our prior observational study has reported associations and trends towards associations between genotypes of the glutamate metabotropic receptor 5 gene (GRM5) and four GP-behaviours, yet the unbalanced representation of GRM5 genotypes occurring in observational studies may have limited the ability to detect associations. Here, we applied a subsampling technique to create a genotypically-balanced dataset in a quasi-manipulative experiment with free ranging cows grazing in steep and rugged terrain of New Zealand's South Island. Using quadratic discriminant analysis, two combinations of eleven GP-behaviours (and a total of fifteen behaviours) were selected to build an exploration model and an elevation model, respectively. Both models achieved ∼ 86% accuracy in correctly discriminating cows' GRM5 genotypes with the training dataset, and the exploration model achieved 85% correct genotype prediction of cows from a testing dataset. Our study suggests a potential pleiotropic effect, with GRM5 controlling multiple grazing behaviours, and with implications for the grazing of steep and rugged grasslands. The study highlights the importance of grazing behavioural genetics in cattle and the potential use of GRM5 markers to select individuals with desired grazing personalities and built herds that collectively utilize steep and rugged rangelands sustainably.

在过去的十年中,牛基因组与放牧行为之间的基因型与表型关联在不同时间和不同环境下都有报道,这表明基因有可能控制肉牛的放牧性格。在用于描述放牧个性行为(GP-behaviours)的大量指标中,目前仍不清楚哪些指标与特定基因有关。我们之前的观察性研究报告了谷氨酸代谢受体 5 基因(GRM5)的基因型与四种 GP 行为之间的关联和关联趋势,但观察性研究中出现的 GRM5 基因型的不平衡可能限制了检测关联的能力。在这里,我们采用了一种子取样技术,在新西兰南岛陡峭崎岖的地形上对自由放牧的奶牛进行了一次准人工实验,以创建一个基因型平衡的数据集。通过二次判别分析,选取了 11 种 GP 行为(共 15 种行为)的两种组合,分别建立了探索模型和海拔模型。这两个模型对训练数据集奶牛 GRM5 基因型的正确判别准确率都达到了 86%,而探索模型对测试数据集奶牛基因型预测的正确率达到了 85%。我们的研究表明,GRM5控制多种放牧行为,具有潜在的多效应,对陡峭崎岖草地的放牧具有影响。这项研究强调了牛放牧行为遗传学的重要性,以及利用 GRM5 标记选择具有理想放牧个性的个体和建立可持续利用陡峭崎岖草场的牛群的可能性。
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Behavior Genetics
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