We demonstrate that CYP2D6 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 CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 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 CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.

我们证明CYP2D6拷贝数变异 (CNV) 可以使用现有的插补算法进行插补。此外，我们报告了芬兰基因瓶颈人群中精神病患者的关键药物遗传学变异的频率。我们将来自乳腺癌疼痛遗传学研究的GWAS 芯片和CYP2D6 CNV 数据结合起来，构建了CYP2D6 CNV 的插补面板 ( n  = 902) 。所得数据集用作来自 SUPER-Finland 研究的 9262 名非相关个体的CYP2D6 CNV 插补面板。基于对 9262 名个体的估算，我们确认了 CYP2D6 超快速代谢物的频率更高，并且UGT1A1的富集率为 22 倍与非芬兰欧洲人相比，芬兰的功能变体 rs4148323 ( UGT1A1 *6) 减少。同样，NUDT15变体 rs116855232 在芬兰高度富集。我们证明了CYP2D6 CNV 的插补是可能的，并且该方法能够在具有全基因组数据的大型生物库中研究CYP2D6。