With respect to the ODunexposed phenotype comparison, we identified rs201123820 in the African-ancestry meta-analysis. This is a non-coding deletion located 2 kb upstream of LOC101928144, an uncharacterized long intergenic non-protein coding RNA. The gene-based association analysis identified a GWS locus in the same region, C18orf32, a gene involved in the activation of the NF-kappaB and MAPK signaling pathways, which play a key role in immune and inflammatory responses53. The phenome-wide analysis in the UK Biobank, despite its being in a predominantly European cohort, showed a significant association of rs201123820 with physical conditions, particularly musculoskeletal disorders. This is particularly interesting as opioids are commonly prescribed for pain management in musculoskeletal disorders and early use is associated with prolonged work disability54, which may be related to the consequences of opioid abuse and/or the severity of the underlying disorder that required treatment. While these associations merit replication, this result highlights how human genetic research can also be relevant to improve pain management protocols.
