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No genome-wide association studies (GWAS) were reported for colorectal polyps and the overlap in polygenic backgrounds conferring risk of colorectal cancer and polyps remains unclear. We performed GWAS on subjects with colorectal polyps using the BioBank Japan data with 4447 cases and 157,226 controls. We evaluated genetic correlations between colorectal polyps and cancer, and effects on colorectal polyps of single nucleotide polymorphisms (SNPs) known to be associated with colorectal cancer. We identified CUX2, a known genetic locus to colorectal cancer, as a susceptibility locus to colorectal polyps (p value = 1.1 × 10−15). Subsequent fine-mapping analysis indicated that rs11065828 in CUX2 is the causal variant for colorectal polyps. We found that known colorectal cancer-susceptible SNPs were also associated with colorectal polyps. The genetic correlation between colorectal cancer and polyps is very high (r = 0.98 and p value = 0.0006). We additionally identified 14 significant loci of colorectal polyps and three significant loci of colorectal cancer by applying the multi-trait analysis of GWAS of colorectal cancer and colorectal polyps. We showed very similar germline polygenic features, which gives us the additional insight into potential cancers at polygenic levels for patients with polyps who are followed up at outpatients’ clinic; thus, close observation and polypectomy is critical to prevent colorectal cancers.

Background The underlying pathology of inguinal hernia is still not fully known; thus, further investigations of genetic backgrounds is needed. Here, we aimed to identify genetic factors attributing to inguinal hernias and explore the polygenic architecture of which some components are population-specific, while others are more common among populations. Methods We performed a genome-wide association study (GWAS) on subjects with inguinal hernias using BioBank Japan (BBJ) data with 1,983 cases and 172,507 controls, followed by a trans-ethnic meta-analysis with UK Biobank (UKBB) data. We performed downstream analyses in order to identify the mechanisms underlying inguinal hernias supported by genetic findings. Findings We identified a locus closest to ELN, which encodes elastin, at the GWAS significant level. The trans-ethnic meta-analysis revealed 23 additional significant loci, including five loci newly identified not significant in BBJ or UKBB GWAS: TGFB2, RNA5SP214/VGLL2, LOC646588, HMCN2, and ATP5F1CP1/CDKN3. Downstream analyses revealed the overlap of GWAS significant signals in extracellular components, including elastin fiber formation. We also found a highly shared polygenic architecture across different populations (trans-ethnic genetic-effect correlation = 0•77, standard error = 0•26) and population-specific lead variants in ELN, indicating the critical role of elastin in inguinal hernias. Interpretation We identified a significant locus of the ELN gene in the Japanese population and five additional loci across different populations. Downstream analyses revealed highly shared genetic architectures across populations and highlighted the important roles of extracellular components in the development of inguinal hernias. These findings deepen our understanding of the mechanisms underlying inguinal hernia. Funding The Japan Agency for Medical Research and Development (AMED) (Grant Number: JP19km0605001)

The identification in a patient of 1 of the 50 variants in the RYR1 or CACNA1S genes reviewed here should lead to a presumption of malignant hyperthermia susceptibility (MHS). MHS can lead to life-threatening reactions to potent volatile anesthetic agents or succinylcholine. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of these agents in patients with these RYR1 or CACNA1S variants (updates at https://cpicpgx.org/guidelines and www.pharmgkb.org).

Objective The aim of this study was to explore the prescription pattern of antiepileptics and the relationship between antiepileptics and adverse drug reactions (ADRs) in a Japanese population. Methods A retrospective observational cohort study was conducted by reviewing the medical records of patients who visited or were admitted to a single tertiary care center between January 2011 and June 2019, were treated with antiepileptics, and developed allergic ADRs associated with these drugs. Results In total, 14,230 unique patients received antiepileptics during the study period. Diazepam was the most frequently used antiepileptic drug (74.8 %), followed by phenobarbital (14.3 %), valproic acid (11.4 %), fosphenytoin (10.0 %), and carbamazepine (7.3 %). Although a trend of increasing prevalence of newer generation antiepileptics was noted, most patients are still treated with older generation antiepileptics. Thirty-two (0.22 %) unique patients experienced ADRs associated with antiepileptics, and the antiepileptic drug most frequently associated with ADRs was carbamazepine, at a rate of 1.4 %. Three patients developed Stevens-Johnson syndrome/toxic epidermal necrolysis, in two of which carbamazepine was implicated. Most patients experienced ADRs associated with aromatic antiepileptics (84.4 %) or older generation antiepileptics (81.3 %). Significance This is the first study to assess the relationship between ADRs and antiepileptics at a tertiary care center in Japan. Based on our results, most patients were prescribed older generation antiepileptics, and most ADR events were linked to the administration of drugs in this category; thus, identification of patients at risk of developing ADRs is critical in order to prevent such events.

Background Albuterol is one of the most frequently used medications in clinical practice and seeing varying responses to albuterol between individuals is not uncommon. Multiple studies have been conducted to investigate the associations of differing responses due to albuterol, particularly with regards to the two nonsynonymous single nucleotide polymorphisms (SNPs) at positions 16 (Arg16Gly: substitution of arginine to glycine at position 16; rs1042713) and 27 (Glu27Gln: substitution of glutamic acid to glutamine at position 27; rs1042714) on the β-2 adrenergic receptor (ADRB2) gene. However, the directions of the correlations are conflicting. Objective The objective of this systematic review and meta-analysis is to assess the effect of the two SNPs on the ADRB2 gene, in terms of the responses that present in asthmatic patients shortly after albuterol inhalation. Methods The primary outcome of this work is a detailed study of the associations of the two SNPs in the ADRB2 gene with treatment response and lung function testing shortly after administration of albuterol to asthmatic patients. A comprehensive literature search, using the OVID platform, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, will be conducted by a specialized librarian without language restrictions. We will include both prospective and retrospective original observational studies, and we will exclude nonhuman or in vitro studies. All abstracts will be reviewed by two authors who will also individually perform data extraction from each eligible study. Any arising disagreements will be resolved through discussion with a third party. Risk of bias for all included studies will be independently assessed using the quality of genetic association studies tool. We will report the systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A narrative synthesis of study results or meta-analyses will be undertaken when appropriate. Results At the moment of writing, we have already started the preliminary literature search and piloting of the study selection process. The anticipated completion date is September 30, 2019. Conclusions Our systematic review and meta-analysis aims to clarify the current evidence of associations between the two nonsynonymous SNPs in the ADRB2 gene and the responses that present in asthmatic patients shortly after albuterol inhalation. If positive correlations are found, this knowledge may be used to improve personalized pharmacotherapy of albuterol use. Trial Registration PROSPERO CRD42019074554; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=74554 International Registered Report Identifier (IRRID) PRR1-10.2196/14759

The purpose of this study was to compare the benefit of neck computed tomography (CT) of identifying important cervical spine injuries (CSIs) with its harm of radiation exposure and cancer risk.A PubMed search for published studies relating to CSI in trauma, cervical spine imaging, CT, and cancer risk was conducted. Article abstracts were reviewed, and selected published studies relating to the study objective were retrieved.Of 100,000 trauma patients, neck CT scans were obtained in 3,767 to 26,785 patients. Of 100,000 patients with trauma on whom a neck CT scan was performed, a CSI was identified in 2,470 to 33,898 patients. Clinically important CSI ranged from 4,724 to 27,119 per 100,000 CT scans. For every 100,000 neck CT scans performed, additional cancer cases occur in a low end estimate of a thyroid cancer cases to a high end estimate of 100 male and 700 female cancer cases. In females, cancer risks are higher than in males, and these are closer to, but still less than, the incidence of clinically important CSI found by CT.CT's benefit of identifying important CSIs in the published studies exceeds its cancer harm risk. However, at their extremes, the numbers are disturbingly close. Limiting neck CT scanning to a higher-risk group would increase the gap between benefit and harm, whereas performing CT routinely on low-risk cases approaches a point where its harm equals or exceeds its benefit.Systematic review, level IV.