Voineskos Aristotle N
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Canada; Institute of Medical Science, University of Toronto, Canada; Department of Psychiatry, University of Toronto, Canada.
Schizophr Res. 2015 Jan;161(1):50-60. doi: 10.1016/j.schres.2014.03.034. Epub 2014 Jun 2.
Schizophrenia is a highly heritable disorder. Thus, the combination of genetics and brain imaging may be a useful strategy to investigate the effects of risk genes on anatomical connectivity, and for gene discovery, i.e. discovering the genetic correlates of white matter phenotypes. Following a database search, I review evidence for heritability of white matter phenotypes. I also review candidate gene investigations, examining association of putative risk variants with white matter phenotypes, as well as the recent flurry of research exploring relationships of genome-wide significant risk loci with white matter phenotypes. Finally, I review multivariate and polygene approaches, which constitute a new wave of imaging-genetics research, including large collaborative initiatives aiming to discover new genes that may predict aspects of white matter microstructure. The literature supports the heritability of white matter phenotypes. Loci in genes intimately implicated in oligodendrocyte and myelin development, growth and maintenance, and neurotrophic systems are associated with white matter microstructure. GWAS variants have not yet sufficiently been explored using DTI-based evaluation of white matter to draw conclusions, although micro-RNA 137 is promising due to its potential regulation of other GWAS schizophrenia genes. Many imaging-genetic studies only include healthy participants, which, while helping control for certain confounds, cannot address questions related to disease heterogeneity or symptom expression, and thus more studies should include participants with schizophrenia. With sufficiently large sample sizes, the future of this field lies in polygene strategies aimed at risk prediction and heterogeneity dissection of schizophrenia that can translate to personalized interventions.
精神分裂症是一种高度可遗传的疾病。因此，遗传学与脑成像相结合可能是一种有用的策略，用于研究风险基因对解剖学连接性的影响，以及用于基因发现，即发现白质表型的遗传相关性。在进行数据库搜索后，我回顾了白质表型遗传性的证据。我还回顾了候选基因研究，检查假定的风险变异与白质表型的关联，以及最近大量探索全基因组显著风险位点与白质表型关系的研究。最后，我回顾了多变量和多基因方法，这些方法构成了成像遗传学研究的新一波浪潮，包括旨在发现可能预测白质微观结构方面的新基因的大型合作计划。文献支持白质表型的遗传性。与少突胶质细胞和髓鞘发育、生长和维持以及神经营养系统密切相关的基因位点与白质微观结构有关。尽管微小RNA 137因其对其他全基因组关联研究精神分裂症基因的潜在调控作用而颇具前景，但基于扩散张量成像对白质的评估尚未充分探索全基因组关联研究变异以得出结论。许多成像遗传学研究仅纳入健康参与者，这虽然有助于控制某些混杂因素，但无法解决与疾病异质性或症状表达相关的问题，因此更多研究应纳入精神分裂症患者。有了足够大的样本量，该领域的未来在于旨在进行精神分裂症风险预测和异质性剖析的多基因策略，这些策略可转化为个性化干预措施。
