controversial (LaForge, Yuferov, & Kreek, 2000; Mague & Blendy, 2010; Sloan et al., 2018). The A118 OPRM1 major allele that codes for the MOR (N40) is found at the highest frequency in individuals of all ethnic backgrounds, and the minor allele G118 OPRM1 (D40 MOR) is found at a lower frequency overall. However, the minor allele SNP occurs in different frequencies in different ethnic groups, from ~3% in African, ~16% in European, and 39–42% in Asian ancestry (Zerbino et al., 2018). There have been several studies aimed at understanding the functional consequences of the MOR D40 variant on receptor activation in mouse models, primates, and humans (Bond et al., 1998; Befort et al., 2001; Beyer, Koch, Schröder, Schulz, & Höllt, 2004; Miller et al., 2004; Zhang, Wang, Johnson, Papp, & Sadée, 2005; Kroslak et al., 2007; Mague et al., 2009; Mague & Blendy, 2010; Mahmoud et al., 2011; Margas, Zubkoff, Schuler, Janicki, & Ruiz-Velasco, 2007). Both animal and human studies reveal that the N40D substitution destroys an N′-terminal glycosylation site and reduces the surface expression for MORs (Ray et al., 2011; Wang, Huang, Ung, Blendy, & Liu-Chen, 2012; Wang, Huang, Blendy, & Liu-Chen, 2014; Halikere et al., 2019). However, another
