title: METAINTER: meta-analysis of multiple regression models in genome-wide association studies.
abstract: BACKGROUND
  Meta-analysis of summary statistics is an essential approach to guarantee the success of genome-wide association studies (GWAS). Application of the fixed or random effects model to single-marker association tests is a standard practice. More complex methods of meta-analysis involving multiple parameters have not been used frequently, a gap that could be explained by the lack of a respective meta-analysis pipeline. Meta-analysis based on combining p-values can be applied to any association test. However, to be powerful, meta-analysis methods for high-dimensional models should incorporate additional information such as study-specific properties of parameter estimates, their effect directions, standard errors and covariance structure.
  
  
  RESULTS
  We modified 'method for the synthesis of linear regression slopes' recently proposed in the educational sciences to the case of multiple logistic regression, and implemented it in a meta-analysis tool called METAINTER. The software handles models with an arbitrary number of parameters, and can directly be applied to analyze the results of single-SNP tests, global haplotype tests, tests for and under gene-gene or gene-environment interaction. Via simulations for two-single nucleotide polymorphisms (SNP) models we have shown that the proposed meta-analysis method has correct type I error rate. Moreover, power estimates come close to that of the joint analysis of the entire sample. We conducted a real data analysis of six GWAS of type 2 diabetes, available from dbGaP (http://www.ncbi.nlm.nih.gov/gap). For each study, a genome-wide interaction analysis of all SNP pairs was performed by logistic regression tests. The results were then meta-analyzed with METAINTER.
  
  
  BACKGROUND
  The software is freely available and distributed under the conditions specified on http://metainter.meb.uni-bonn.de.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Vaitsiakhovich
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Drichel
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Herold
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Lacour
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
mesh_terms: D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D059647:Gene-Environment Interaction; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012984:Software