ranked score above the specified threshold percentile, is calculated. This observed statistic is then compared to 1,000,000 randomly permuted pathways of identical size. This generates an empirical GSEA P-value for each pathway. Significance was determined when an individual pathway reached a false discovery rate (FDR) < 0.05 in either analysis (Supplementary table 9). In total, 2529 pathways from Gene Ontology, PANTHER, KEGG and Ingenuity were tested for enrichment of multiple modest associations with age at menarche.