Plummer Jasmine T, Gordon Alexis J, Levitt Pat
Institute for the Developing Mind, The Saban Research Institute, Children's Hospital Los Angeles , Los Angeles, CA , USA.
Keck School of Medicine, University of Southern California , Los Angeles, CA , USA.
Front Psychiatry. 2016 Aug 22;7:142. doi: 10.3389/fpsyt.2016.00142. eCollection 2016.
Most psychiatric disorders are considered neurodevelopmental, and the associated genes often are expressed in tissues outside of the brain. This suggests a biological relatedness with medical co-occurrences that could have broad clinical implications for diagnosis and patient management over a lifetime. A qualitative integration of public data from genetic consortia of psychiatric disorders and medical comorbidities explores the question of whether genetically associated psychiatric illnesses present with co-occurring disturbances can be used to define specific mental-physical health relations. Novel patterns of gene-disorder relations appear with approximately one-third of conservatively defined, consortia-generated candidate risk genes with multiple psychiatric diagnoses. Moreover, nearly as many genes overlap with non-psychiatric phenotypes, including cardiovascular, renal, respiratory, and metabolic disturbances. While the landscape of genetic risk will change as study populations are expanded and biological confirmations accrue, the current relationships suggest that a mostly siloed perspective of gene relatedness to one categorical psychiatric diagnosis is not clinically useful. The future holds the promise that once candidates are fully validated, genome screening and mutation identification will bring more precision for predicting the risk for complex health conditions. Our view is that as genetic data are refined, continuing to decipher a shared pattern of genetic risk for brain and peripheral organ pathophysiology is not simply an academic exercise. Rather, determining relatedness will impact predictions of multifaceted health risks, patient treatment, and management.
大多数精神疾病被认为是神经发育性的,相关基因通常在大脑以外的组织中表达。这表明与医学共病存在生物学关联,这可能对一生的诊断和患者管理具有广泛的临床意义。对来自精神疾病和医学合并症基因联盟的公共数据进行定性整合,探讨了与共发性障碍相关的基因性精神疾病是否可用于定义特定的心理-身体健康关系这一问题。基因-疾病关系的新模式出现在约三分之一经保守定义、由联盟生成的具有多种精神疾病诊断的候选风险基因中。此外,几乎同样多的基因与非精神疾病表型重叠,包括心血管、肾脏、呼吸和代谢紊乱。虽然随着研究人群的扩大和生物学确认的积累,遗传风险格局将会改变,但目前的关系表明,将基因相关性主要局限于一种分类精神疾病诊断的观点在临床上并无用处。未来有望实现的是,一旦候选基因得到充分验证,基因组筛查和突变鉴定将为预测复杂健康状况的风险带来更高的精准度。我们的观点是,随着遗传数据的完善,继续解读大脑和外周器官病理生理学的遗传风险共享模式不仅仅是一项学术活动。相反,确定相关性将影响对多方面健康风险的预测、患者治疗和管理。