Genome-wide association study identifies a potent locus associated with human opioid sensitivity.

Candidate locus possibly associated with human opioid sensitivity. (a) Illustration of the genes in the genomic region from position 208 000 000 to 208 300 000 on chromosome 2 in the HapMap database (http://hapmap.ncbi.nlm.nih.gov/index.html.ja; accessed 1 March 2012). (b) Fine mapping of the candidate region after the imputation-based association analysis. The circle, square and triangle plots represent the results from the additive, dominant and recessive models, respectively. The area between the dotted vertical lines represents the genomic position from 208 070 000 to 208 240 000 on chromosome 2. (c) State of linkage disequilibrium (LD) between the SNPs in the genomic position from 208 070 000 to 208 240 000 on chromosome 2, based on the genotype data of the subjects who are derived from the Japanese population and underwent cosmetic orthognathic surgery. Numbers in squares in which two SNPs face represent the percentage of the r2 values calculated from the genotype data of the SNPs. Squares with asterisks represent r2=1. Only the values >0.70 are highlighted.

Association analysis between opioid analgesic requirements and the rs2952768 SNP. (a) Total dose of analgesics administered per body weight (μg kg–1; log transformed) during the 24-h postoperative period after cosmetic orthognathic surgery (mandibular sagittal split ramus osteotomy). (b) Total dose of analgesics administered per body weight (μg kg–1; log transformed) during the 24-h postoperative period after major open abdominal surgery. *Q<0.05, greater dose of analgesic administered in the C/C genotype compared with the T/C and T/T genotypes with genome-wide significance; †P<0.05, greater dose of analgesic administered in the C/C genotype compared with the T/C and T/T genotypes with nominal significance. The data are expressed as mean±s.e.m.

Relative mRNA expression level of the candidate genes between each genotype subgroup of the rs2952768 SNP in post-mortem brains. (a) Results for the METTL21A gene. (b) Results for the CREB1 gene. NS, no significant association between relative mRNA expression and genotype subgroup (P⩾0.05); *P<0.05, greater level of mRNA expression in the C/C genotype compared with the T/C and T/T genotypes with nominal significance. The data are expressed as mean±s.e.m.