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风险倾向及其神经基础的遗传性: 行为遗传学和影像遗传学研究
其他题名Heritability of risk-taking propensity and its neural basis: behavior genetics and imaging genetics study
郑党
学位类型硕士
导师周媛
2015
学位授予单位中国科学院大学
学位授予地点北京
学位专业理学
关键词风险倾向 神经基础 遗传性 行为遗传学 影像遗传学 双生子
摘要风险倾向即承担风险的意向存在个体差异,并且与导致负性结果的行为相关。研究遗传因素对风险倾向及其神经基础的影响,有助于理解风险倾向个体差异产生的生物学基础,从而发展有效的方法对高风险行为进行预防和干预。针对这一研究目的,本研究综合采用行为遗传学和影像遗传学的分析方法,结合双生子模型分析、荟萃分析、静息态功能磁共振技术研究了成年双生子风险倾向的遗传性及风险倾向神经基础的遗传性。具体而言:
    研究1采用行为遗传学的研究方法,研究了仿真气球风险决策任务〔Balloon Analogue Risk Task, BART〕所测量的风险倾向的遗传性。该研究纳入了239对成年双生子(同卵149对;异卵90对),采用双生子单变量遗传模型分析遗传和环境因素对BART风险倾向的影响。研究发现,AE模型为最优拟合模型,其中遗传贡献为41%,非共享环境贡献为59%。该研究提示,风险倾向具有中等程度的遗传性,其个体差异来自遗传和非共享环境。
    研究2采用影像遗传学的研究方法,研究了与BART风险倾向相关的静息态脑功能活动的遗传性。首先,通过荟萃分析确定了BART任务中一致激活的脑区。选取激活概率最大即在以往研究中最一致被激活的脑区作为种子区,在110对成年双生子(同卵61对;异卵49对)中,采用基于种子区的静息态功能连接分析,确定与BART风险倾向显著相关的脑功能连接,继而采用基于体素的双生子单变量遗传模型分析确定与BART风险倾向相关的静息态脑功能连接的遗传性。进一步,采用基于体素的双生子双变量遗传模型分析BART风险倾向与静息态脑功能活动的遗传相关性。荟萃分析发现,右侧前脑岛在以往采用BART任务的fM RI研究中激活概率最大;以右侧前脑岛为种子区的静息态功能连接分析发现,右侧前脑岛与双侧额中回、右侧额上回、楔前叶之间的功能连接与BART任务测量的风险倾向有显著相关;双生子模型分析发现,与BART风险倾向相关的右侧前脑岛一右侧额中回、右侧前脑岛一左侧额中回、右侧前脑岛一右侧额上回的静息态功能连接具有可遗传性(最高遗传度分别为43%,  50%, 42% ),并且右侧前脑岛一右侧额中回的功能连接与BART衡量的风险倾向存在遗传相关,提示二者有重叠的遗传基础。
    总体上,我们发现风险倾向及其神经基础具有一定程度的遗传性,其个体差异来源于遗传和非共享环境。这些发现有助于理解风险倾向个体差异产生的生物学基础,为寻找药物滥用等具有负性结果的高风险行为的内表型提供科学依据,并为发展有效的方法预防和干预高风险行为提供理论基础。
其他摘要Propensity  of  risk  taking  has  been  linked  with  behaviors  with  adverse consequences such as substance abuse, accidents, and gambling.  Clarifying genetic influence on the neural basis underlying this risk-taking propensity can be useful to understand the biological basis leading to individual differences of risky  propensity.  It's  helpful  to  prevent  or  ameliorate  potential  adverse consequences associated with risk taking. For this purpose, this study adopted behavior  genetics  and  imaging  genetics  methods,  combining twins meta-analysis and resting-state fMRI to investigate the heritability of risky propensity and its neural basis among adult twins.
In study 1, we conducted a behavior genetics study to evaluate the heritability of risk-taking propensity measured by Balloon Analogue Risk Task (BART), a computerized, laboratory-based tool. Recruiting 239(MZ: 149,DZ: 90) pairs of adult twins, we tested genetic and  environmental influence on risk-taking propensity with univariate model fitting analysis. We found AE model was more desirable, and gene accounted for about 41% contribution of the variation in risk-taking behavior,  while the  other  59%  could  be  explained  by unique environment. The result indicated that risk-taking propensity was moderately heritable, and variation of individual differences came from the contribution of gene and unique environment.
In study 2, we assessed the heritability of risk-taking propensity in BART from insight of imaging genetics. First, we conducted a meta-analysis of the fMRI studies which used BART to measure actual risk taking behavior. We found several regions associated with risk behavior, Adjusted Pumps, in BART. Among these regions, right anterior insula was the most activated, so we selected it as region of interest (ROI). Next, ROI-based resting-state functional connectivity (RSFC) analysis in 110 (MZ: 61, DZ: 49) pairs of twins could identify regions which are correlated with the risk-taking propensity measured by the BART.
After voxel-based univariate model fitting to estimate the heritability of neural basis underlying risk-taking propensity, we conducted voxel-based bivariate model fitting to determine to which extent the BART risk-taking propensity and its neural basis are genetic correlated. The results showed that the RSFCs of the right  anterior  insula  (aINS)  related  to  the  risk-taking  propensity  were significantly heritable. In addition, genes influencing the BART also moderately influenced the functional connectivities between the right aINS and the right lateral prefrontal cortices.
In summary, in the current study we find risk-taking propensity measured by the BART and its neural correlates are both heritable, and the variation of individual difference came from gene and environment. This study provides evidence for the BART and RSFC to be considered as an endophenotype for genetic studies of risky behaviors with adverse consequences, and these findings should facilitate discovery of gene variants influencing the risk-taking propensity, potentially opening up new avenues in the prevention or amelioration of potential adverse consequences associated with risk taking.
学科领域行为遗传学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/19801
专题社会与工程心理学研究室
作者单位中国科学院心理研究所
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郑党. 风险倾向及其神经基础的遗传性: 行为遗传学和影像遗传学研究[D]. 北京. 中国科学院大学,2015.
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