Polygenic risk and white matter integrity in individuals at high risk of mood disorder.
Polygenic risk and white matter integrity in individuals at high risk of mood disorder.
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DOI：
10.1016/j.biopsych.2013.01.027
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发表时间：
2013-08-15
影响因子：
10.6
通讯作者：
McIntosh, Andrew M.
中科院分区：
文献类型：
--
作者：
Whalley, Heather C.;Sprooten, Emma;Hackett, Suzanna;Hall, Lynsey;Blackwood, Douglas H.;Glahn, David C.;Bastin, Mark;Hall, Jeremy;Lawrie, Stephen M.;Sussmann, Jessika E.;McIntosh, Andrew M.
关键词：
双相情感障碍（BD）和重度抑郁症（MDD）是高度遗传和基因重叠的疾病，其特征是情绪的发作性升高和/或抑郁。两者都表现出白质完整性的异常，使用扩散张量磁共振成像（MRI）测量，这也是遗传性的。然而，目前尚不清楚这些异常如何与每种疾病的潜在遗传结构相关。全基因组关联研究（GWAS）已经证明多基因对双相障碍和重度抑郁症有显著的影响，其中风险归因于许多影响较小的等位基因的总和。确定总体多基因风险概况评分对神经影像学异常的影响可能有助于确定遗传易感性的替代措施，从而为风险预测模型提供信息。在目前的研究中，我们确定了情绪障碍（BD和MDD）潜在风险的常见遗传变异与分数各向异性（白质完整性指数）的关系程度。研究对象是有家族性情绪障碍风险的未受影响个体（n=70）和比较对象（n=62）。根据精神病学基因组联盟的GWAS数据，分别计算双相障碍和重度抑郁症的多基因风险评分。我们报道，MDD的高多基因风险等位基因负荷与两组中白质完整性下降显著相关，在右侧上纵束中达到峰值。这些发现表明，检查脑成像数据的多基因方法可能是识别与情绪障碍遗传风险相关的特征的有用手段。
Bipolar disorder (BD) and major depressive disorder (MDD) are highly heritable and genetically overlapping conditions characterised by episodic elevation and/or depression of mood. Both demonstrate abnormalities in white matter integrity, measured using diffusion tensor magnetic resonance imaging (MRI), that are also heritable. However it is unclear how these abnormalities relate to the underlying genetic architecture of each disorder. Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to BD and MDD, where risk is attributed to the summation of many alleles of small effect. Determining the effects of an overall polygenic risk profile score on neuroimaging abnormalities may help to identify proxy measures of genetic susceptibility and thereby inform models of risk prediction. In the current study we determined the extent to which common genetic variation underlying risk to mood disorders (BD and MDD) was related to fractional anisotropy, an index of white matter integrity. This was conducted in unaffected individuals at familial risk of mood disorder (n=70) and comparison subjects (n=62). Polygenic risk scores were calculated separately for BD and MDD based on GWAS data from the Psychiatric Genome Consortia. We report that a higher polygenic risk allele load for MDD was significantly associated with decreased white matter integrity across both groups in a large cluster with a peak in the right-sided superior longitudinal fasciculus. These findings suggest that the polygenic approach to examining brain imaging data may be a useful means of identifying traits linked to the genetic risk of mood disorders.
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