A research team led by Prof. LI Ming from Kunming Institute of Zoology, Chinese Academy of Sciences, in collaboration with Prof. FANG Yiru in Shanghai Mental Health Center and other researchers, performed an exploration of the genetic architecture of bipolar disorder in Han Chinese populations from Chinese mainland. An editorial comment highlighted the significant contribution of their study to the understanding of genetic basis of bipolar disorder. The study was published in JAMA Psychiatry on December 2, 2020.
Characterized by fluctuations in mood states, behaviors and energy levels, bipolar disorder is a highly heterogenic and heritable complex psychiatric illness. Patients diagnosed with bipolar disorder are usually suffered from impaired emotion and cognition, which significantly affect their daily lives and even survival. However, the lack of knowledge of the genetic and biological basis of bipolar disorder has hindered successful diagnosis and management of this illness, resulting in misdiagnosis and delayed diagnosis, difficulties in eradication of the illness, and varied responses to medications. Therefore, lots of endeavors have been made to elucidate the etiology of bipolar disorder. So far, accumulating evidence supports a significant genetic component in its pathogenesis, and studies have identified multiple polymorphisms or genes involved in this illness. Nevertheless, these studies were conducted primarily in Europeans and Japanese populations. Given that different continental populations usually have different genetic backgrounds as a result of their specific local environmental conditions and population histories, examining genetic factors involved in bipolar disorder in Chinese populations is urgently needed.
To gain insights into the genetic basis of bipolar disorder in Chinese, Dr. LI Ming and his team initiated extensive collaborations with multiple health care providers and research institutions all over the country. They have recruited 1822 bipolar disorder patients and 4650 healthy controls from multiple provinces and cities in China for this study.
A genome-wide association study (GWAS) was performed to characterize polymorphisms correlated with the onset of bipolar disorder. They have found several polymorphisms significantly associated with the risk of bipolar disorder in Chinese subjects, and identified a risk gene TMEM108. They then carried out a meta-analysis and polygenic risk score analysis in the Chinese sample and samples of other world populations. Their analysis further identified multiple genes involved in bipolar disorder pathogenesis, and confirmed that there was substantial risk genetic overlap between Chinese and Europeans. Furthermore, this study also suggested that multiple psychiatric illnesses (i.e., schizophrenia, depression) and traits such as cognitive functions in humans could be attributed to some common genetic foundation with bipolar disorder, providing essential information for dissecting the mechanisms underlying different psychiatric illnesses and relevant phenotypes.
This study, entitled “Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis” , was published in JAMA Psychiatry and was accompanied by an editorial comment on December 2, 2020. Web link:https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2773733. Dr. LI Ming, Dr. FANG Yiru are the co-corresponding authors, and Dr.LI Huijuan, Dr. ZHANG Chen and Dr. HUI Li are the co-first authors in this paper. Dr. LUO Xiongjian and Dr. YAO Yonggang have provided constructive help and support. This study was financially supported by grants from the National Natural Science Foundation of China (NSFC) etc.
Genetic basis of bipolar disorder (Imaged by LI Ming)
(By LI Ming, Editor: YANG Yingrun)
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