Table 3.
Associations of previously implicated OPRM1 intron 1 SNPs with heroin addiction across the cohorts used in the current study (Urban Health Study, CIDR – Gelernter Study, and the Australian Heroin Dependence Study). These SNPs were reported for having nominally to statistically significant associations with heroin addiction (N=412 cases and 184 controls, comprised of European Americans or Israelis with Jewish ancestry) (12), opioid dependence (N=91 cases and 338 controls, comprised of all European Americans) (19), or heroin dependence (N=1,459 cases and 531 controls, comprised of Australians of European ancestry) (10). None of these SNPs were previously tested for independent replication. SNPs are sorted by meta-analysis P value.
| SNP (Min or Allele) | Ref. | Previously reported P | Urban Health Study, African Americans (N=1,293 cases and 2,369 controls) | Urban Health Study, European Americans (N=711 cases and 6,384 controls) | CIDR – Gelernter Study, African Americans (N=307 cases and 545 controls) | Australian Heroin Dependence Study, Australians of European ancestry (N=1,293 cases and2,369 controls) | Meta-analysis P | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MAF | P | OR (95% CI) | MAF | P | OR (95% CI) | MAF | P | OR (95% CI) | MAF | P | OR (95% CI) | ||||
| rs3823010 (A) |
(19) | 0.001 | 0.12 | 0.025 | 1.19 (1.02-1.37) |
0.16 | 8.6 ×10−4 |
1.28 (1.11-1.49) |
0.13 | 0.17 | 1.25 (0.91-1.72) |
0.17 | 2.4× 10−4 |
1.23 (1.10-1.37) |
2.7× 10−8 |
| rs3778151 (C)a |
(10, 12) |
0.003 (12) 0.031 (10) |
0.29 | 0.029 | 1.12 (1.01-1.27) |
0.16 | 3.0 ×10−3 |
1.25 (1.08-1.45) |
0.31 | 0.33 | 1.12 (0.89-1.41) |
0.17 | 3.2× 10−4 |
1.23 (1.10-1.37) |
2.4× 10−7 |
| rs524731 (A)a |
(19) | 0.011 | 0.12 | 0.065 | 1.15 (0.99-1.33) |
0.21 | 1.4 ×10−3 |
1.25 (1.09-1.43) |
0.12 | 0.17 | 1.25 (0.91-1.75) |
0.21 | 3.7× 10−3 |
1.16 (1.05-1.29) |
1.2× 10−6 |
| rs511435 (T)a |
(19) | 0.002 | 0.20 | 0.15 | 1.10 (0.97-1.23) |
0.21 | 1.4 ×10−3 |
1.25 (1.09-1.43) |
0.19 | 0.17 | 1.20 (0.93-1.59) |
0.21 | 3.7× 10−3 |
1.16 (1.05-1.29) |
3.0× 10−6 |
| rs495491 (G)a,b |
(19) | 0.002 | 0.52 | 0.015 | 1.14 (1.02-1.25) |
0.26 | 8.2 ×10−3 |
1.19 (1.04-1.35) |
0.52 | 0.25 | 1.14 (0.91-1.43) |
not available |
not available |
not available |
1.8 ×10−4,c |
| rs510769 (T) |
(12) | 0.0008 | 0.24 | 0.97 | 1.00 (0.89-1.12) |
0.26 | 1.0 ×10−2 |
1.19 (1.04-1.35) |
0.24 | 0.29 | 1.15 (0.88-1.52) |
0.26 | 8.4× 10−3 |
1.14 (1.03-1.25) |
7.0× 10−4 |
These SNPs were not available as genotyped SNPs in the Heroin Dependence GWAS, so the following SNPs in high linkage disequilibrium were used: rs514980 as a proxy SNP for both rs511435 and rs524731 (r2=1 and D′=1 in 1000 Genomes EUR) and rs3778153 as a proxy SNP for rs3778151 (r2=0.98 and D′=1 in 1000 Genomes EUR). The best proxy for rs495491 was the other previously reported SNP rs510769 (r2=0.98 and D′=1 in 1000 Genomes EUR).
For rs495491, G is the minor allele in populations of European ancestry, but A is the minor allele in African Americans. The presented allele frequencies correspond to the G allele.
Meta-analysis was computed using the results that were available.