title: Resequencing three candidate genes discovers seven potentially deleterious variants susceptibility to major depressive disorder and suicide attempts in Chinese.
abstract: BACKGROUND
  To date almost 200 genes were found to be associated with major depressive disorder (MDD) or suicide attempts (SA), but very few genes were reported for their molecular mechanisms. This study aimed to find out whether there were common or rare variants in three candidate genes altering the risk for MDD and SA in Chinese.
  
  
  METHODS
  Three candidate genes (HOMER1, SLC6A4 and TEF) were chosen for resequencing analysis and association studies as they were reported to be involved in the etiology of MDD and SA. Following that, bioinformatics analyses were applied on those variants of interest.
  
  
  RESULTS
  After resequencing analysis and alignment for the amplicons, a total of 34 common or rare variants were found in the randomly selected 36 Hong Kong Chinese patients with both MDD and SA. Among those, seven variants show potentially deleterious features. Rs60029191 and a rare variant located in regulatory region of the HOMER1 gene may affect the promoter activities through interacting with predicted transcription factors. Two missense mutations existed in the SLC6A4 coding regions were firstly reported in Hong Kong Chinese MDD and SA patients, and both of them could affect the transport efficiency of SLC6A4 to serotonin. Moreover, a common variant rs6354 located in the untranslated region of this gene may affect the expression level or exonic splicing of serotonin transporter. In addition, both of a most studied polymorphism rs738499 and a low-frequency variant in the promoter region of the TEF gene were found to be located in potential transcription factor binding sites, which may let the two variants be able to influence the promoter activities of the gene.
  
  
  CONCLUSIONS
  This study elucidated the potentially molecular mechanisms of the three candidate genes altering the risk for MDD and SA. These findings implied that not only common variants but rare variants could make contributions to the genetic susceptibility to MDD and SA in Chinese.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Shitao
authors.initials: S
authors.lastname: Rao
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Cherry She Ting
authors.initials: CS
authors.lastname: Leung
authors.affiliation: Department of Psychiatry, Shatin Hospital, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Macro Hb
authors.initials: MH
authors.lastname: Lam
authors.affiliation: Department of Psychiatry, Shatin Hospital, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Yun Kwok
authors.initials: YK
authors.lastname: Wing
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Electronic address: mary-waye@cuhk.edu.hk.
authors.forename: Mary Miu Yee
authors.initials: MM
authors.lastname: Waye
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. Electronic address: kwtsui@cuhk.edu.hk.
authors.forename: Stephen Kwok Wing
authors.initials: SK
authors.lastname: Tsui
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D003865:Major Depressive Disorder / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D000072233:Homer Scaffolding Proteins / Q000235:genetics* / Q000378:metabolism; D006723:Hong Kong; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011401:Promoter Regions, Genetic; D012306:Risk; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D013406:Suicide, Attempted / Q000208:ethnology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C000606614:HOMER1 protein, human; D000072233:Homer Scaffolding Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C489490:TEF protein, human; D012701:Serotonin
keywords: Bioinformatics prediction; Common or rare variants; Major depressive disorder; Resequencing analysis; Suicide attempts; Transcription factor binding sites