Zhang Tianxiao, Hou Liping, Chen David T, McMahon Francis J, Wang Jen-Chyong, Rice John P
Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University, Shaanxi, China.
Human Genetics Branch, The National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
Gene. 2018 Mar 1;645:119-123. doi: 10.1016/j.gene.2017.12.025. Epub 2017 Dec 14.
Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance.
双相情感障碍是一种终生患病率约为1%的精神疾病。先前的基因研究已经确定了多个可能与双相情感障碍相关的染色体连锁区域和候选基因。本研究旨在使用来自一个四代家族的6个相关病例样本，确定双相情感障碍的潜在易感变异体。采用外显子组测序和连锁分析相结合的方法，确定双相情感障碍的潜在易感变异体。我们的研究确定了一份包含五个双相情感障碍潜在候选基因的清单。在这五个基因中，GRID1（谷氨酸受体δ-1亚基）特别有意思，该基因先前已被报道与几种精神疾病和大脑相关特征有关。在我们的双相情感障碍家系中，从两个表亲身上鉴定出了该基因中具有功能意义的变异体。我们的研究结果表明，这些基因及相关罕见变异体在这个家族双相情感障碍的发病和发展中可能发挥作用。需要进一步的研究来重复这些发现，并评估它们的病理生物学意义。
