We conducted within-family association analyses in four sibling cohorts (22,135 sibling pairs) and compared the resulting estimates to those from a meta-analysis that excluded the siblings (N = 1,070,751). The latter association statistics were adjusted for stratification bias using the LD Score intercept. Fig. 2 shows the observed sign concordance for three sets of approximately independent SNPs, selected using P value cutoffs of 5×10−3, 5×10−5, and 5×10−8. The concordance is substantially greater than expected by chance but weaker than predicted by our Bayesian framework, even after we extend the framework to account for inflation in GWAS coefficients due to assortative mating. In a second analysis based on all SNPs, we estimate that within-family effect sizes are roughly 40% smaller than GWAS effect sizes and that our assortative-mating adjustment explains at most one third of this deflation. (For comparison, when we apply the same method to height, we found that the assortative-mating adjustment fully explains the deflation of the within-family effects.)
