BC Children's Hospital Research Institute, Vancouver, BC, V5Z 4H4, Canada.
Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.
Pharmacogenomics. 2021 Apr;22(5):251-261. doi: 10.2217/pgs-2020-0130. Epub 2021 Mar 26.
To improve the identification and interpretation of pharmacogenetic variants through the integration of disease and drug-related traits. We hypothesized that integrating genome-wide disease and pharmacogenomic data may drive new insights into drug toxicity and response by identifying shared genetic architecture. Pleiotropic variants were identified using a methodological framework incorporating colocalization analysis. Using genome-wide association studies summary statistics from the UK Biobank, European Bioinformatics Institute genome-wide association studies catalog and the Pharmacogenomics Research Network, we validated pleiotropy at the locus between allopurinol response and gout and identified novel pleiotropy between antihypertensive-induced new-onset diabetes, Crohn's disease and inflammatory bowel disease at the locus. New mechanistic insights and genetic loci can be uncovered by identifying pleiotropy between disease and drug-related traits.
通过整合疾病和药物相关特征来提高对药物遗传变异的识别和解释。我们假设，通过确定共同的遗传结构，整合全基因组疾病和药物基因组学数据可能会通过识别共享的遗传结构，为药物毒性和反应提供新的见解。使用包含共定位分析的方法框架来识别多效性变体。利用来自英国生物库、欧洲生物信息学研究所全基因组关联研究目录和药物基因组学研究网络的全基因组关联研究汇总统计数据，我们在别嘌醇反应和痛风之间的 基因座上验证了多效性，并在 基因座上发现了抗高血压药物引起的新发糖尿病、克罗恩病和炎症性肠病之间的新多效性。通过识别疾病和药物相关特征之间的多效性，可以揭示新的机制见解和遗传基因座。
