芬兰精神病患者中 CYP2D6拷贝数估算小组的实施情况和关键药物基因变异的频率

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2022-02-23 DOI:10.1038/s41397-022-00270-y

Katja Häkkinen, Johanna I. Kiiski, Markku Lähteenvuo, Tuomas Jukuri, Kimmo Suokas, Jussi Niemi-Pynttäri, Tuula Kieseppä, Teemu Männynsalo, Asko Wegelius, Willehard Haaki, Kaisla Lahdensuo, Risto Kajanne, Mari A. Kaunisto, Annamari Tuulio-Henriksson, Olli Kampman, Jarmo Hietala, Juha Veijola, Jouko Lönnqvist, Erkki Isometsä, Tiina Paunio, Jaana Suvisaari, Eija Kalso, Mikko Niemi, Jari Tiihonen, Mark Daly, Aarno Palotie, Ari V. Ahola-Olli

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引用次数: 3

摘要

我们证明，CYP2D6拷贝数变异（CNV）可以用现有的估算算法进行估算。此外，我们还报告了芬兰基因瓶颈人群中精神病患者的关键药物基因变异频率。我们结合了乳腺癌疼痛遗传学研究中的 GWAS 芯片和 CYP2D6 CNV 数据，构建了一个 CYP2D6 CNV 的估算面板（n = 902）。由此产生的数据集作为 CYP2D6 CNV 推算面板，用于来自芬兰超级研究的 9262 名非相关个体。根据对 9262 名个体的估算，我们证实芬兰人与非芬兰裔欧洲人相比，CYP2D6 超快速代谢者的频率更高，UGT1A1 功能减弱变体 rs4148323 (UGT1A1*6) 的富集度为 22 倍。同样，NUDT15 变体 rs116855232 在芬兰也高度富集。我们的研究表明，CYP2D6 CNV 的估算是可行的，而且这种方法能够在具有全基因组数据的大型生物库中研究 CYP2D6。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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

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.

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.