Extended Data Figure 3. LD Score regression consistent with polygenic inheritance.

The relationship between marker χ² association statistics and linkage disequilibrium (LD) as measured by the LD Score. LD Score is the sum of the r² values between a variant and all other known variants within a 1 cM window, and quantifies the amount of genetic variation tagged by that variant. Variants were grouped into 50 equal-sized bins based on LD Score rank. LD Score Bin and Mean χ² denotes mean LD score and test statistic for markers each bin. We simulated (Supplementary Text) test statistics under two scenarios: (a) no true association, inflation due to population stratification (b) polygenic inheritance (λ_GC =1.32), in which we assigned independent and identically distributed per-normalized-genotype effects to a randomly selected subset of variants. Panel (c) present results from the PGC schizophrenia GWAS (λ_GC =1.48). The real data are strikingly similar to the simulated data summarized in (b) but not (a). The intercept estimates the inflation in the mean χ² that results from confounding biases, such as cryptic relatedness or population stratification. Thus, the intercept of 1.066 for the schizophrenia GWAS suggests that ~90% of the inflation in the mean χ² results from polygenic signal. The results of the simulations are also consistent with theoretical expectation (see Supplementary Text).