title: Prediction of serotonin transporter promoter polymorphism genotypes from single nucleotide polymorphism arrays using machine learning methods.
abstract: BACKGROUND
  The serotonin transporter gene (SLC6A4) and its promoter (5-HTTLPR) polymorphism have been the focus of a large number of association studies of behavioral traits and psychiatric disorders. However, large-scale genotyping of the polymorphism has been very difficult. We report the development and validation of a 5-HTTLPR genotype prediction model.
  
  
  METHODS
  The single nucleotide polymorphisms (SNPs) from the 2000 kb region surrounding 5-HTTLPR were used to construct a prediction model through a newly developed machine learning method, multicategory vertex discriminant analysis with 2147 individuals from the Northern Finnish Birth Cohort genotyped with the Illumina 370K SNP array and manually genotyped for 5-HTTLPR polymorphism. The prediction model was applied to SNP genotypes in a Dutch/German schizophrenia case-control sample of 3318 individuals to test the association of the polymorphism with schizophrenia.
  
  
  RESULTS
  The prediction model of eight SNPs achieved a 92.4% accuracy rate and a 0.98±0.01 area under the receiving operating characteristic. Evidence for an association of the polymorphism with schizophrenia was observed (P=0.05, odds ratio=1.105).
  
  
  CONCLUSIONS
  This prediction model provides an effective substitute of manually genotyped 5-HTTLPR alleles, providing a new approach for large scale association studies of this polymorphism.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7088, USA.
authors.forename: Ake Tzu-Hui
authors.initials: AT
authors.lastname: Lu
authors.forename: Steven
authors.initials: S
authors.lastname: Bakker
authors.forename: Esther
authors.initials: E
authors.lastname: Janson
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D001185:Artificial Intelligence; D020029:Base Pairing / Q000235:genetics; D030541:Databases, Genetic; D060005:Genotyping Techniques / Q000379:methods*; D005858:Germany; D006801:Humans; D008957:Models, Genetic; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins