Abstract
We imputed four variable number tandem repeat polymorphisms (VNTRs) and one moderating single nucleotide polymorphism (SNP) in SLC6A3, DRD4, SLC6A4, and MAOA in 486,551 UK Biobank individuals. Using the HRC-imputed data, we phased a 3Mb window surrounding the target polymorphism using Shapeit2 (Delaneau et al. 2013). We then imputed the target polymorphisms using Minimac3 (Das et al. 2016). Our reference panel for imputation included two independent samples, 1) the Family Transitions Project (FTP), and 2) the combined Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) (Conger et al. 2012, Derringer et al. 2015, Young et al. 2000), which had previously been genotyped on various Illumina and Affymetrix platforms and had directly-genotyped VNTR genotypes, as previously described (Derringer et al. 2015, Haberstick et al. 2014, 2015). As the reference panels were genotyped on various platforms, we first imputed the reference panels to the HRC and restricted the analysis to biallelic SNPs with imputation INFO scores of at least 0.6. For MAOA, on the X chromosome, we imputed males and females separately. We used the two independent reference panels (FTP and CADD/GADD) with both genome-wide SNP data and directly-genotyped VNTR data to estimate our imputation accuracy. Genotypic match rates were above 0.8 for all polymorphisms and for both datasets. Applying a genotype probabilities threshold of 0.99 increased the minimum genotypic match rate to 0.96. In the UK Biobank individuals, the Minimac3 INFO scores were 0.925 for the SLC6A3 VNTR, 0.906 for the DRD4 VNTR, 0.907 for SLC6A4 rs25531, 0.883 for SLC6A4 5HTTLPR, and 0.968 for MAOA VNTR
1 Application
Application ID | Title |
16651 | Genetic architecture of disease and related anthropometric phenotypes |
1 Return
Return ID | App ID | Description | Archive Date |
2154 | 16651 | Imputation of behavioral candidate gene repeat variants in 486,551 publicly-available UK Biobank individuals | 2 Apr 2020 |