DESCRIPTION:
Credible set analysis using FINEMAP in TUD-EUR analysis. We conducted independent GWAS of TUD cases and controls in individuals of European (EUR) ancestry across four PsycheMERGE sites (BioVU, MGBB, PMBB, and MVP) and performed a GWAS meta-analysis. We defined cases as patients who received at least two TUD ICD-9 or −10 codes (corresponding to the phecode definition) in their medical records, and controls as patients who had no TUD diagnosis codes. TUD-EUR included 11,422,241 imputed SNPs in a cohort of 163,734 TUD cases and 331,271 controls, which is 8.5 times larger than the total sample size of previous nicotine dependence GWAS. Genome-wide significant (GWS) loci were defined as those with p<5.00E-08 with LD r2>0.1, within a 1MB window, based on the structure of the Haplotype Reference Consortium (HRC) multi-ancestry reference panel for the multi-ancestry meta-analysis, or the HRC ancestry-appropriate reference panel otherwise. To identify TUD risk loci and lead SNPs, we performed linkage-disequilibrium (LD) clumping in FUMA using a range of 3 Mb, r2 >0.1, and the respective ancestry 1000 Genome reference panel. Genomic risk loci that were located <1Mb apart were incorporated into a single locus. For loci that harbored multiple variants, we used conditional & joint association analysis using GWAS summary statistics (COJO) in Genome-wide Complex Trait Analysis (GCTA) software to define independent variants by conditioning them on the most significant variant within each locus. Following conditioning, significant variants (p<5.00E-08) were considered independent. We determined credible variants among the independent variants by merging risk variants within 1Mb of the lead variant and fine-mapped the resulting region with 95% credible sets using FINEMAP. All loci from the credible set analysis are shown here. From supplementary table 11.
LABEL:
Potential causal SNP loci TUD-EUR_r2
SCORE TYPE:
Correlation
THRESHOLD:
<= 0.5
GENES IN THRESHOLD:
0
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Genes in threshold: 0
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