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Chunk #26 — Methods — Polygenic risk scores and statistical analyses

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Polygenic risk scores for smoking: predictors for alcohol and cannabis use?
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The polygenic risk scores reflect a combined effect of a number of selected Single Nucleotide Polymorphisms (SNPs) (38). Different p-value thresholds (Pt) of 0.1, 0.2 and 0.5 were used to define large sets of ‘risk alleles’ in the discovery sample (from TAG meta-analyses summary-level data). Those sets of risk alleles are used to generate a polygenic risk score for individuals in an independent target sample from the NTR. The individual risk score is calculated by multiplying the number of risk alleles per SNP (0,1,2) with the regression coefficient from the GWA meta-analyses, summed over all SNPs in the considered set of SNPs (42). The individual polygenic risk scores for the NTR participants were calculated using PLINK, with commands: --bfile NTRfile --maf 0.01 --mind 0.1 --geno 0.1 --hwe 0.000001 --score TAG_AOS_P5.dat --out TAG_AOSp5. Only SNPs that overlapped between the TAG sample and the NTR sample were included (Table 1).