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Chunk #56 — Online Methods — Replication of GWAS loci

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Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.
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For the sign test, we first identified the overlapping SNPs present in the ADHD GWAS and each of the three replication analyses (i.e. deCODE, 23andMe, and EAGLE/QIMR). For each replication cohort intersecting SNPs were then clumped for LD (r2 > 0.05 within 1 Mb) for all variants with P < 1 × 10−4 in the ADHD GWAS (or P < 1 × 10−5 for the deCODE replication) using 1000 Genomes Phase 3 data on European ancestry populations. After clumping, sign tests were performed to test the proportion of loci with a concordant direction of effect in the replication cohort (π) using a one sample test of the proportion with Yates’ continuity correction129 against a null hypothesis of π = 0.50 (i.e. the signs are concordant between the two analyses by chance) in R130. This test was evaluated separately for concordance in deCODE, 23andMe, and EAGLE/QIMR for loci passing P-value thresholds of P < 5 × 10−8 (i.e. genome-wide significant loci), P < 1 × 10−7, P < 1 × 10−6, P < 1 × 10−5, and P < 1 × 10−4 in the ADHD GWAS meta-analysis (Supplementary Information).