Imputation of behavioral candidate gene repeat variants in 486,551 publicly-available UK Biobank individuals

Eur J Hum Genet. 2019 Jun;27(6):963-969. doi: 10.1038/s41431-019-0349-x. Epub 2019 Feb 5.


Some of the most widely studied variants in psychiatric genetics include variable number tandem repeat variants (VNTRs) in SLC6A3, DRD4, SLC6A4, and MAOA. While initial findings suggested large effects, their importance with respect to psychiatric phenotypes is the subject of much debate with broadly conflicting results. Despite broad interest, these loci remain absent from the largest available samples, such as the UK Biobank, limiting researchers' ability to test these contentious hypotheses rigorously in large samples. Here, using two independent reference datasets, we report out-of-sample imputation accuracy estimates of >0.96 for all four VNTR variants and one modifying SNP, depending on the reference and target dataset. We describe the imputation procedures of these candidate variants in 486,551 UK Biobank individuals, and have made the imputed variant data available to UK Biobank researchers. This resource, provided to the scientific community, will allow the most rigorous tests to-date of the roles of these variants in behavioral and psychiatric phenotypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biological Specimen Banks*
  • Genetic Loci*
  • Genome-Wide Association Study
  • Genotype*
  • Humans
  • Mental Disorders / genetics*
  • Minisatellite Repeats*
  • Polymorphism, Single Nucleotide*
  • United Kingdom