机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of theChinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China[2]KunmingCollege of Life Science, University of Chinese Academy of Sciences, Kunming,Yunnan, China[3]Peking University Sixth Hospital/Institute of Mental Health,Beijing, China[4]NHC Key Laboratory of Mental Health (Peking University) andNational Clinical Research Center for Mental Disorders (Peking University SixthHospital), Beijing, China[5]State Key Laboratory of Cognitive Neuroscience andLearning, IDG/McGovern Institute for Brain Research, Beijing Normal University,Beijing, China[6]Department of Psychiatry, Ningbo Kangning Hospital, Ningbo,Zhejiang, China[7]Shanghai Mental Health Center, Shanghai Jiao TongUniversity School of Medicine, Shanghai, China[8]Wuhan Institute forNeuroscience and Neuroengineering, South-Central University for Nationalities,Wuhan, Hubei, China[9]Chinese Brain Bank Center, Wuhan, Hubei, China[10]Psychiatry Department, The first people’s hospital of Yunnan province,Kunming, Yunnan, China内科片临床心理科云南省第一人民医院[11]CAS Center for Excellence in Brain Science andIntelligence Technology, Chinese Academy of Sciences, Shanghai, China[12]KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in CommonDiseases, Kunming, Yunnan, China[13]Center for Excellence in Animal Evolutionand Genetics, Chinese Academy of Sciences, Kunming, Yunnan, China[14]Peking-Tsinghua Joint Center for Life Sciences and PKU IDG/McGovernInstitute for Brain Research, Peking University, Beijing, China
Major depressive disorder (MDD) is recognized as a primary cause of disability worldwide, and effective management of this illness has been a great challenge. While genetic component is supposed to play pivotal roles in MDD pathogenesis, the genetic and phenotypic heterogeneity of the illness has hampered the discovery of its genetic determinants. In this study, in an independent Han Chinese sample (1824 MDD cases and 3031 controls), we conducted replication analyses of two genetic loci highlighted in a previous Chinese MDD genome-wide association study (GWAS), and confirmed the significant association of a single nucleotide polymorphism (SNP) rs12415800 near SIRT1. Subsequently, using hypothesis-free whole-brain analysis in two independent Han Chinese imaging samples, we found that individuals carrying the MDD risk allele of rs12415800 exhibited aberrant gray matter volume in the left posterior cerebellar lobe compared with those carrying the non-risk allele. Besides, in independent Han Chinese postmortem brain and peripheral blood samples, the MDD risk allele of rs12415800 predicted lower SIRT1 mRNA levels, which was consistent with the reduced expression of this gene in MDD patients compared with healthy subjects. These results provide further evidence for the involvement of SIRT1 in MDD, and suggest that this gene might participate in the illness via affecting the development of cerebellum, a brain region that is potentially underestimated in previous MDD studies.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81722019, 31701133, 81825009, 81571313]; Yunnan Applied Basic Research Projects [2018FB051]; National Key R&D Program of China [2016YFC1307000]; medical and health science and technology project in Zhejiang [2018KY721]; Major Science and Technology Projects in Ningbo, Zhejiang Province, China [2017C510012]; Medical Science and Technology Project in Ningbo, Zhejiang Province, China [2017A10]; Chinese Academy of Sciences Western Light Program; Youth Innovation Promotion Association, CAS; CAS Pioneer Hundred Talents Program; 1000 Young Talents ProgramChinese Academy of Sciences; Takeda Pharmaceuticals Company Limited; F. Hoffman-La Roche Ltd; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01MH085542, R01MH093725, P50MH066392, P50MH080405, R01MH097276, RO1-MH-075916, P50M096891, P50MH084053S1, R37MH057881, R37MH057881S1, HHSN271201300031C, AG02219, AG05138, MH06692]; [U01MH103392]; [U01MH103365]; [U01MH103346]; [U01MH103340]; [U01MH103339]; [R21MH109956]; [R21MH105881]; [R21MH105853]; [R21MH103877]; [R21MH102791]; [R01MH111721]; [R01MH110928]; [R01MH110927]; [R01MH110926]; [R01MH110921]; [R01MH110920]; [R01MH110905]; [R01MH109715]; [R01MH109677]; [R01MH105898]; [R01MH094714]; [P50MH106934]; [U01MH116488]; [U01MH116487]; [U01MH116492]; [U01MH116489]; [U01MH116438]; [U01MH116441]; [U01MH116442]; [R01MH114911]; [R01MH114899]; [R01MH114901]; [R01MH117293]; [R01MH117291]; [R01MH117292]
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of theChinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China[2]KunmingCollege 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 theChinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China[2]KunmingCollege of Life Science, University of Chinese Academy of Sciences, Kunming,Yunnan, China[3]Peking University Sixth Hospital/Institute of Mental Health,Beijing, China[4]NHC Key Laboratory of Mental Health (Peking University) andNational Clinical Research Center for Mental Disorders (Peking University SixthHospital), Beijing, China[11]CAS Center for Excellence in Brain Science andIntelligence Technology, Chinese Academy of Sciences, Shanghai, China[14]Peking-Tsinghua Joint Center for Life Sciences and PKU IDG/McGovernInstitute for Brain Research, Peking University, Beijing, China
推荐引用方式(GB/T 7714)：
Weipeng Liu,Hao Yan,Danyang Zhou,et al.The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population[J].TRANSLATIONAL PSYCHIATRY.2019,9:doi:10.1038/s41398-019-0675-3.
APA：
Weipeng Liu,Hao Yan,Danyang Zhou,Xin Cai,Yuyanan Zhang...&Xiao Xiao.(2019).The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population.TRANSLATIONAL PSYCHIATRY,9,
MLA：
Weipeng Liu,et al."The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population".TRANSLATIONAL PSYCHIATRY 9.(2019)
医学