Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder

Abstract

<p>We demonstrate that <i>CYP2D6 </i>copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and <i>CYP2D6 </i>CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (<i>n </i>= 902) for <i>CYP2D6 </i>CNV. The resulting data set was used as a <i>CYP2D6</i> CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of <i>CYP2D6 </i>ultrarapid metabolizers and a 22-fold enrichment of the <i>UGT1A1</i> decreased function variant rs4148323 (<i>UGT1A1</i>*6) in Finland compared with non-Finnish Europeans. Similarly, the <i>NUDT15</i> variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of <i>CYP2D6</i> CNV is possible and the methodology enables studying <i>CYP2D6</i> in large biobanks with genome-wide data.<br></p>