DESCRIPTION:
120 lead SNPs (88 independent loci) for the tobacco use disorder cross-ancestry meta-analysis ("TUD-multi"). The primary multi-ancestry meta-analysis of 20,801,211 imputed SNPs (lambda λGC=1.141, Figure 2) was performed on seven cohorts from four U.S. biobanks, comprising 653,790 individuals with TUD phecode data available, with 75.71% EUR, 17.50% AA, and 6.79% LA. 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. All genome-wide significant loci had been reported by prior smoking GWAS (Supplementary Table 7), including aspects of smoking initiation (88/88), age of initiation (14/88), consumption (38/88), cessation (48/88) and nicotine dependence (1/88; Supplementary Figure 2, Supplementary Figure 3). While all these loci were recently discovered in a GWAS of 3.4 million individuals in the GSCAN study, here we reproduce some of the GSCAN findings with a considerably smaller sample size. 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 LD clumping in FUMA41 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. From supplementary table 7.
LABEL:
Lead SNP loci TUD-multi_pvalue
SCORE TYPE:
P-Value
THRESHOLD:
<= 0.5
GENES IN THRESHOLD:
83
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ABSTRACT:
Genes in threshold: 83
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