| Application: | 33722, Identifying precision drug treatments by linking phenotype and genotype in drug response |
| Title: | Pharmacogenetics at scale: An analysis of the UK Biobank |
| Size: | 38.3 MB |
| Archived: | 27 Apr 2021 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
Return 3388
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Notes
Pharmacogenetics (PGx) studies the influence of genetic variation on drug response. Clinically actionable associations inform guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), but the broad impact of genetic variation on entire populations is not well-understood. We analyzed PGx allele and phenotype frequencies for 487,409 participants in the U.K. Biobank, the largest PGx study to date. For fourteen CPIC pharmacogenes known to influence human drug response, we find that 99.5% of individuals may have an atypical response to at least one drug; on average they may have an atypical response to 12 drugs. Non-European populations carry a greater frequency of variants that are predicted to be functionally deleterious; many of these are not captured by current PGx allele definitions. Strategies for detecting and interpreting rare variation will be critical for enabling broad application of pharmacogenetics.Application 33722
Identifying precision drug treatments by linking phenotype and genotype in drug response
We seek access to the UK Biobank in order to improve understanding of drug response and generate hypotheses of drug-genotype and drug-phenotype combinations for precision medicine. We plan to use the resources available to 1) examine the landscape of drug prescriptions and the co-occurrence with other medications, diseases, and phenotypes, 2) explore how genetics and sex relates to patterns of drug prescription and disease, and 3) develop guidelines for prescriptions based on our findings. Our work will lead to improved understanding of the contributions of drugs to disease progression and will also generate hypotheses about effective treatments. The UK Biobank?s stated purpose includes improving the treatment of illness. Prescription drugs are the primary treatment for many diseases, and treatment efficacy determines patient outcome. The proposed research focuses on examining the landscape of drug prescriptions and indications, and identifying drug-drug, drug-gene, and drug-sex associations with health-related phenotypes. Identifying these associations will lead to hypotheses about treatment indications and mechanisms that could improve drug prescriptions and development. Additionally, highlighting interactions that lead to unfavorable responses can help prevent negative health outcomes caused by drugs or drug combinations that are ineffective or dangerous. We will characterize the landscape of drug prescriptions and their co-occurrence with other drugs and diseases in the UK Biobank. We will perform genome-wide association studies to look for genetic associations with drug prescriptions, disease, and phenotypes related to drug response. Sex and hormone effects will be examined to highlight genetic variants with sex-specific effects, and to test for significant interactions that affect drug related outcomes. We would like to use the full cohort for our research.
| Lead investigator: | Professor Russ Altman |
| Lead institution: | Stanford University |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3389 | Pharmacogenetics at Scale: An Analysis of the UK Biobank | Gregory McInnes (+5) | 2020 | Clinical Pharmacology & Therapeutics |
Enabling scientific discoveries that improve human health