Table 1.
Lead GWAS significant variants
| European Ancestry | African Ancestry | Cross-ancestry | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| rsID | chr | A1 | position | Genomic SEM Beta | GenomicSEM P | SusieR SNPs in Credible set | FUMA GWAS SNPs | ASSET Beta | ASSET p | METASOFT Beta | METASOFT p |
| rs1937455 | 1 | A | 66416939 | 0.013 | 7.74E-09 | 2 | 43 | 0.024 | 3.00E-03 | 0.013 | 0.100 |
| rs1475064 | 1 | A | 73882478 | 0.014 | 3.06E-09 | 3 | 161 | 0.09 | 6.25E-03 | 0.011 | 0.051 |
| rs2860846 | 1 | T | 174075924 | 0.014 | 3.37E-09 | 34 | 36 | NA | NA | NA | NA |
| rs1260326 | 2 | T | 27730940 | −0.015 | 7.60E-10 | 17 | 10 | NA | NA | NA | NA |
| rs570436 | 2 | C | 45142673 | −0.015 | 1.31E-09 | 15 | 8 | NA | NA | NA | NA |
| rs2717054 | 2 | G | 58046683 | −0.014 | 1.97E-08 | 8 | 44 | NA | NA | NA | NA |
| rs55855024 | 3 | C | 16850764 | −0.014 | 2.37E-08 | 8 | 35 | NA | NA | NA | NA |
| rs6795772 | 3 | C | 49365269 | 0.014 | 1.58E-09 | 2 | 265 | NA | NA | NA | NA |
| rs3114045 | 4 | T | 100252560 | −0.023 | 1.85E-10 | 3 | 134 | −0.019 | 0.554 | −0.012 | 2.60E-15 |
| rs1662031 | 4 | A | 100256793 | −0.015 | 1.17e-09 | 3 | 134 | NA | NA | NA | NA |
| rs1813006 | 4 | G | 103001649 | 0.037 | 3.18E-12 | 9 | 11 | NA | NA | NA | NA |
| rs864882 | 9 | C | 127968109 | 0.015 | 3.41E-08 | 2 | 26 | NA | NA | NA | NA |
| rs7073987 | 10 | C | 110565868 | 0.015 | 2.04E-08 | 3 | 61 | NA | NA | NA | NA |
| rs2861190 | 11 | C | 38517941 | −0.014 | 3.66E-08 | 5 | 117 | NA | NA | NA | NA |
| rs17602038 | 11 | T | 113364691 | 0.017 | 6.64e-12 | 2 | 117 | NA | NA | NA | NA |
| rs6589386 | 11 | C | 113443753 | 0.017 | 2.92E-12 | 2 | 65 | NA | NA | NA | NA |
| rs10083370 | 14 | G | 104314182 | 0.014 | 1.53E-09 | 3 | 89 | NA | NA | NA | NA |
| rs28567725 | 16 | T | 53826028 | 0.016 | 2.50E-10 | 5 | 83 | 0.012 | .457 | 0.007 | 6.49E-12 |
| rs2424952 | 20 | T | 31685873 | 0.030 | 3.21E-08 | 2 | 4 | NA | NA | NA | NA |
Lead GWAS variants from European ancestry addiction-rf meta-analysis (in Genomic SEM), African ancestry addiction-rf meta-analysis (based on ASSET), and trans-ancestry meta-analysis (in METASOFT) of the common SNPs underlying PAU, PTU, CUD, and OUD. We generated 4 cross-substance meta-analyses. First, we used a model that leverages genetic overlap across different SUDs via genomic SEM (Figure 1). The GWAS of European ancestry individuals, run with GSEM, forms the primary analysis for most downstream analyses (i.e., TWAS, genetic correlation, PheWAS, genetic causality). The GSEM results for the addiction-rf are shown first (Genomic SEM Beta, Genomic SEM p); the number of credible SNPs in each set (SusieR; r2= .6) with GWAS lead SNPs (from FUMA) are also shown. Next, results for the cross-substance meta-analysis in African ancestry individuals, using ASSET, is shown (ASSET Beta, ASSET p). ASSET splits groups of SNPs into pleiotropic versus non-pleiotropic SNPs, which produces a sparser set of GWAS results (as all SNPs must be pleiotropic to estimate a Beta and P-value), hence, NAs. Finally, to conduct a cross-ancestry meta-analysis, we applied ASSET to the European ancestry sample and then meta-analyzed the European and African ancestry summary data using METASOFT (METASOFT beta, METASOFT p; see Table 2). Direction of all betas corresponds to the effect allele (A1). rsID=rs number, chr=Chromosome, A1=effect allele, position=bp genomic position. Significance is set at Bonferroni corrected genome-wide significance in a two-sided test (P < 5e-8).