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Chunk #5 — Results

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Defining the role of common variation in the genomic and biological architecture of adult human height.
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Our family based analyses also provided strong evidence that the inflated statistics are driven predominantly by the highly polygenic nature of height. We assessed whether variants that reached genome-wide significance after single GC correction replicated in family-based analyses of up to 25,849 samples (effective sample size 14,963, using methods that are immune to stratification (Online Methods, Supplementary Note, and Supplementary Tables 5 and 6). We identified genome-wide significant associations from a meta-analysis that excluded the family-based samples, and tested these associations for replication in the family-based samples; a lower rate of replication than expected could be due to inflation of effect sizes in the discovery sample from the “winner’s curse” and/or stratification. Of 416 genome-wide significant SNPs representing multiple signals selected after exclusion of family-based studies, 371 SNPs had a consistent direction of effect (compared with 208 expected by chance, and 400 expected in the absence of any inflation of estimated effect sizes), and 142 replicated with P<0.05 (compared with 21 expected by chance, and 210 expected in the absence of effect size inflation; Supplementary Table 5). These analyses (particularly