title: NR4A2 genetic variation and Parkinson's disease: Evidence from a systematic review and meta-analysis.
abstract: The homo sapiens nuclear receptor subfamily 4, group A (NR4A2) genetic variation has been implicated as a risk factor for Parkinson's disease (PD). Nevertheless, the results are inconclusive. We conducted a comprehensive systematic review and meta-analysis to quantify the impact of NR4A2 variation on the risk of PD.
  
  
  
  All eligible case-control studies published up to June 2016 by searching Pubmed, OVID, EBSCO, PsycINFO, ISI Web of Knowledge, Chinese Biomedical Literature Database and China Academic Journals Database were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of the association in fixed- or random-effects model.
  
  
  
  Eighteen studies reported 24 genetic variants with a total of 6150 cases and 5919 controls were included. Twelve studies for NR4A2 rs35479735 polymorphism and 4 studies for rs12803 were available for meta-analysis. A significant association was observed for rs35479735 under the homozygous model (OR=1.31, 95% CI: 1.10-1.56, P=0.003), whereas no significant association for rs12803 was detected. In subgroup analysis stratified by ethnicity, age onset and familial history, we found no significant association except one in sporadic PD subgroup under the recessive (OR=3.30, 95% CI: 1.23-8.84, P=0.02) and homozygous model (OR=3.43, 95% CI: 1.26-9.33, P=0.02) for rs35479735.
  
  
  
  The study comprehensively evaluated the association of NR4A2 variation with PD, and the results failed to demonstrate that the NR4A2 polymorphisms significantly associated with PD except for rs35479735, suggesting that more studies are needed to elucidate if NR4A2 is a risk of PD.
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Loudi Center Hospital, Loudi City 417000, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Department of Geriatric Psychiatry, Changning Mental Health Center, Shanghai 200042, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: College of Health and Rehabilitation Sciences (Sargent College), Boston University, Boston, MA 02215, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Cui
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Ren
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Xiujia
authors.initials: X
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: yushuny@gmail.com.
authors.forename: Shunying
authors.initials: S
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: chunbo_li@163.com.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D019317:Evidence-Based Medicine; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics*; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017678:Sex Distribution
chemical_list: D005819:Genetic Markers; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2
keywords: Meta-analysis; NR4A2; Parkinson's disease (PD); Systematic review