Polygenic Risk Scores: Coming to Your Operating Room?

This is the authors' abstract. We don't add key points for this paper.

Assessment of postoperative nausea and vomiting (PONV) risk and development of mitigation strategies is an essential part of any anesthetic plan.PONV is a significant concern in perioperative care, impacting patient recovery, satisfaction, and healthcare resources.The past hundred years have been spent understanding the pathophysiologic factors and developing novel therapeutic and mitigation strategies.While it is common to elicit a patient's family history of PONV during routine preoperative evaluation, surprisingly, little is known about the genetics of PONV risk apart from small studies on several hundred patients with inconsistent findings.1,2 This gap in our knowledge presents an opportunity to explore the role of genetic risk in preoperative decision-making.In this issue, Douville et al. 3 develop a risk prediction model using clinical and genetic risk factors.They use two large cohorts of 39,261 and 25,262 patients, respectively, from independent academic centers to perform a genome-wide association study (GWAS), which allows them to investigate the genetic variations in the structure of individual genes over a cohort of 5,703 patients who developed PONV vs 58,820 who did not.In contrast to Mendelian diseases, such as malignant hyperthermia and pseudocholinesterase deficiency, in which a defect in a single gene can lead to the manifestation of the disease, polygenic disease risk is shared between multiple genes and contributes partially to common disease conditions.In these cases, small DNA structure variations known as single nucleotide polymorphisms (SNPs) exhibit small effects individually but collectively can influence disease risk.In this study, Douville et al. 3 test the association between 42,124,633 genetic variants and the risk of PONV, with 16,564,986 variants present in both cohorts.Due to the large number of independent comparisons, the P value threshold that is considered significant in these studies is 5×10 -8, and in this study, there was only one rare variant (rs760998109) that met that criterion; since the variant was investigated only in one of the cohorts, these results could not be replicated in the second cohort and necessitate future validation.