机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.[2]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.[3]The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.[4]Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.[5]Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, Henan, China.[6]Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China.[7]Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[8]Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, Hubei, China.[9]Chinese Brain Bank Center, Wuhan, Hubei, China.[10]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan, China.[11]CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.[12]Henan Province People’s Hospital, Zhengzhou, Henan, China
Recent European genome-wide association studies (GWAS) have revealed strong statistical correlations between MDD and numerous zero-to-high linked variants in the genomic region containing major histocompatibility complex (MHC) genes (MHC region), but the underlying biological mechanisms are still unclear. To better understand the roles of this genomic region in the neurobiology of MDD, we applied a convergent functional genomics approach to integrate GWAS data of MDD relevant biological phenotypes, gene-expression analyses results obtained from brain samples, and genetic analyses of independent Chinese MDD samples. We observed that independent MDD risk variants in the MHC region were also significantly associated with the relevant biological phenotypes in the predicted directions, including the emotional and cognitive-related phenotypes. Gene-expression analyses further revealed that mRNA expression levels of several MHC region genes in the human brain were associated with MDD risk SNPs and diagnostic status. For instance, a brain-enriched gene ZNF603P consistently showed lower mRNA levels in the individuals carrying MDD risk alleles and in MDD patients. Remarkably, we further found that independent MDD risk SNPs in the MHC region likely converged to affect the mRNA level(s) of the same gene(s), and Europeans and Han Chinese populations have a substantial shared genetic and molecular basis underlying MDD risk associations in the MHC region. These results highlighted several potential pivotal genes at the MHC region in the pathogenesis of MDD. Their common impacts on multiple psychiatric relevant phenotypes also implicated the neurological processes shared by different psychological processes, such as mood and/or cognition, shedding lights on their potential biological mechanisms.
基金：
Strategic Priority Research Program
of the Chinese Academy of Sciences (Grant no. XDB13000000 to
ML), National Natural Science Foundation of China (Grant nos.
81722019 to ML, 31701133 to XX, 31701088 to LL, 81871067 to
HC, 81671330 to LX-L, 31730037 to Y-GY, 81471358 to CZ, and
81771450 to CZ), Yunnan Applied Basic Research Projects
(2018FB051 to XX, 2018FB136 to HC), the Medical and Health
Science and Technology project in Zhejiang (2018KY721 to DSZ),
Shanghai Municipal Education Commission—Gaofeng Clinical
Medicine Grant Support (20152530 to CZ), the Shanghai Municipal
Commission of Health and Family Planning Foundation, Key
Developing Disciplines (2015ZB0405 to CZ), the High Scientific
and Technological Research Fund of Xinxiang Medical University
(Grant no. 2017ZDCG-04 to LX-L), the Medical science and
technology research project of Henan Province (201702131 to
YF-Y), the Fundamental and Advancing Foundation of Henan
Province (132300413216 to LX-L), the Training plan for young
excellent teachers in Colleges and Universities of Henan (No.
2016GGJS-106 to WQ-L), the Science and technology project of
Xinxiang (CXGG17030 to WQ-L), and the support project for the
Disciplinary group of Psychiatry and Neuroscience, Xinxiang
Medical University. Xiao Xiao was also supported by the Chinese
Academy of Sciences Western Light Program, and Youth Innovation
Promotion Association, CAS. Ming Li was also supported by
CAS Pioneer Hundred Talents Program and the 1000 Young
Talents Program.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|1 区医学
小类|1 区药学2 区神经科学2 区精神病学
最新[2025]版：
大类|2 区医学
小类|1 区药学2 区神经科学2 区精神病学
第一作者：
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.[2]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.[2]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.[4]Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.[5]Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, Henan, China.[11]CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.[12]Henan Province People’s Hospital, Zhengzhou, Henan, China
推荐引用方式(GB/T 7714)：
Li Huijuan,Chang Hong,Song Xueqin,et al.Integrative analyses of major histocompatibility complex loci in the genome-wide association studies of major depressive disorder.[J].Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.2019,44(9):1552-1561.doi:10.1038/s41386-019-0346-3.
APA：
Li Huijuan,Chang Hong,Song Xueqin,Liu Weipeng,Li Lingyi...&Li Ming.(2019).Integrative analyses of major histocompatibility complex loci in the genome-wide association studies of major depressive disorder..Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,44,(9)
MLA：
Li Huijuan,et al."Integrative analyses of major histocompatibility complex loci in the genome-wide association studies of major depressive disorder.".Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 44..9(2019):1552-1561
医学