Further analyses were performed for the SNPs carried forward for replication. Each of these analyses is described in detail in the “Supplementary Note”. In brief, we performed: 1) a conditional genome-wide association analysis to examine whether any of the 82 BMD loci harbored additional independent signals; 2) tested gene-by-gene pair-wise interactions between these BMD loci; 3) assessed within the independent setting of the PERF study (for details on study design see Supplementary Tables 20A, 20B & 20C) the predictive ability derived from the cumulative effect of the 63 genome-wide significant autosomal BMD SNPs in relation to BMD levels and osteoporosis risk; and that of the 16 BMD SNPs also associated with fracture risk in relation to fracture risk; 4) identified SNPs having r2 ≥ 0.80 with the lead SNP that were potentially functional (nonsense, nonconservative non-synonymous, synonymous, exonic splicing, transcription factor binding sites, etc) using regional imputation with the 1000 Genomes data (June 2010 release); 5) tested the relationship between gene expression profiles from a) trans-iliacal bone biopsies and BMD in 84 unrelated postmenopausal women49 and b) also examined cis-
