title: Population-specific genotype imputations using minimac or IMPUTE2.
abstract: In order to meaningfully analyze common and rare genetic variants, results from genome-wide association studies (GWASs) of multiple cohorts need to be combined in a meta-analysis in order to obtain enough power. This requires all cohorts to have the same single-nucleotide polymorphisms (SNPs) in their GWASs. To this end, genotypes that have not been measured in a given cohort can be imputed on the basis of a set of reference haplotypes. This protocol provides guidelines for performing imputations with two widely used tools: minimac and IMPUTE2. These guidelines were developed and used by the Genome of the Netherlands (GoNL) consortium, which has created a population-specific reference panel for genetic imputations and used this reference to impute various Dutch biobanks. We also describe several factors that might influence the final imputation quality. This protocol, which has been used by the largest Dutch biobanks, should take approximately several days, depending on the sample size of the biobank and the computer resources available.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: van Leeuwen
authors.affiliation: 1] University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands. [2] University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Kanterakis
authors.affiliation: 1] University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands. [2] University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
authors.forename: Patrick
authors.identifier: 0000000256543966
authors.initials: P
authors.lastname: Deelen
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, the Netherlands.
authors.forename: Mathijs V
authors.initials: MV
authors.lastname: Kattenberg
authors.affiliation: 1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: 1] Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands. [2] Department of Epidemiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Paul I W
authors.identifier: 0000000177357858
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: 1] University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands. [2] University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: 1] University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands. [2] University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
authors.forename: Morris A
authors.initials: MA
authors.lastname: Swertz
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, the Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. [2] PolyOmica, Groningen, the Netherlands.
authors.forename: Lennart C
authors.identifier: 000000021959342X
authors.initials: LC
authors.lastname: Karssen
authors.affiliation: Department of Biological Psychology, VU University, Amsterdam, the Netherlands.
authors.forename: Jouke Jan
authors.initials: JJ
authors.lastname: Hottenga
mesh_terms: D055106:Genome-Wide Association Study; D006239:Haplotypes; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D012984:Software