title: A haplotype in the 5'-upstream region of the NDUFV2 gene is associated with major depressive disorder in Han Chinese.
abstract: BACKGROUND
  There is ample evidence supporting the idea that mitochondrial dysfunction and altered expression of complex I subunits play important roles in the pathophysiology of mental disorders. Early literature reports have implicated NDUFV2, a nuclear-encoded mitochondrial complex I subunit gene, in bipolar disorder and schizophrenia. There has been no genetic study to investigate whether there is an association between NDUFV2 and major depressive disorder (MDD).
  
  
  METHODS
  This study recruited 744 patients with MDD and 767 well-matched healthy controls in a Chinese Han population, and genotyped 9 SNPs within NDUFV2.
  
  
  RESULTS
  Initial analysis showed statistically significant differences for 2 SNPs (rs4798765 and rs12964485) in the genotypic distribution and for 1 SNP (rs4797356) in the allelic distribution between the case and control groups. Nevertheless, no significance was demonstrated following multiple testing corrections. Haplotype analysis showed that the T-C haplotype, consisting of rs12457810 and rs12964485, was significantly associated with MDD (P=0.005, corrected P=0.04 after a 10,000 permutation test). We performed an eQTL analysis and found that rs12964485 was significantly associated with NDUFV2 expression in the occipital cortex (P=0.036), albeit this significance did not survive after Bonferroni correction.
  
  
  CONCLUSIONS
  This is a preliminary investigation with a relatively modest sample size.
  
  
  CONCLUSIONS
  Our findings provided preliminary evidence that a haplotype T-C consisting of rs12457810 and rs12964485 in the 5'-upstream region of NDUFV2 may be a protective factor for the development of MDD in Han Chinese.
authors.affiliation: Department of Psychiatry, Jinhua Second Hospital, Zhejiang, China.
authors.forename: Zaifu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Tongde Hospital of Zhejiang Province, Zhejiang, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Psychiatry, Tongde Hospital of Zhejiang Province, Zhejiang, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Hangzhou Seventh People's Hospital, Zhejiang, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Tang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Yunnan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, Jinhua Second Hospital, Zhejiang, China; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Yunnan, China; Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zhangchen645@gmail.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009245:NADH Dehydrogenase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics
chemical_list: D009245:NADH Dehydrogenase; C492562:NDUFV2 protein, human
keywords: 5′-Upstream; Han Chinese; Major depression disorder; NDUFV2; SNP