Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.

We did not find a significant sex difference in overall PRS effects (OR male = 4.70 (4.16–5.31), OR female = 5.28 (4.80–5.80), P difference = 0.141, two-sample two-sided Z -test), even though the effect of sex was highly significant (OR = 2.54 (2.33–2.78), P = 1.93 × 10 −94 , one-sample two-sided Z -test).

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Despite the considerably smaller sample size, 71% of the lead SNPs from the pooled discovery meta-analysis were at least nominally significant in the replication dataset ( P < 0.05) and there was a high positive correlation between the effect size estimates of the discovery stage and the replication dataset (Pearson’s r = 0.94, P < 2.2 × 10 −16 ; Extended Data Fig. 6a ).

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