Functional annotation of this finding corroborated a substantial role for ADGRV1 in increasing OD risk, especially the potential pathogenic effects of variation in AGDRV1 on cardio-cerebral mechanisms, which could contribute to the risk of fatal opioid overdose or respiratory depression that has been observed following high-dose opioid exposure. This evidence concerns the gene ADGRV1 and Respiratory insufficiency due to muscle weakness.