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Chunk #72 — ONLINE METHODS: — Testing for population stratification

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Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.
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To assess the extent to which population stratification may bias our GWAS estimates, we conducted three tests. First, we estimated LD Score intercepts using the summary statistics of the discovery and replication GWAS of general risk tolerance and of the GWAS of our four main risky behaviors and their first PC12. Second, following Okbay et al. (2016)10, we conducted sign tests that compare the signs of the estimates from our discovery GWAS of general risk tolerance (but excluding all full siblings from the UKB cohort) to the signs of the estimates from within-family (WF) GWAS of general risk tolerance. If our discovery GWAS estimates were entirely driven by stratification, then the signs of the WF estimates—which are immune to stratification—should be independent of the signs of the discovery GWAS estimates, in which case we would expect a sign concordance of roughly 50%. A higher degree of sign concordance would suggest that at least some of the signal from the GWAS comes from true genetic effects. Across four sign tests, we strongly reject the null hypothesis of 50% sign concordance for