Heritability estimates for all bone phenotypes were 30–66%. LOD scores ≥3.0 were found on chromosomes 15 (1.5 LOD confidence interval: 51,336,679–58,934,236 bp) and 22 (35,890,398–48,603,847 bp) for femoral shaft section modulus. The ten primary phenotypes had 12 associations with 100K SNPs in GEE models at p < 0.000001 and 2 associations in FBAT models at p < 0.000001. The 25 most significant p-values for GEE and FBAT were all less than 3.5 × 10
-6 and 2.5 × 10
-5, respectively. Of the 40 top SNPs with the greatest numbers of significantly associated BMD traits (including femoral neck, trochanter, and lumbar spine), one half to two-thirds were in or near genes that have
not previously been studied for osteoporosis. Notably, pleiotropic associations between BMD and bone geometric traits were uncommon. Evidence for association (FBAT or GEE p < 0.05) was observed for several SNPs in candidate genes for osteoporosis, such as rs1801133 in
MTHFR; rs1884052 and rs3778099 in
ESR1; rs4988300 in
LRP5; rs2189480 in
VDR; rs2075555 in
COLIA1; rs10519297 and rs2008691 in
CYP19, as well as SNPs in
PPARG (rs10510418 and rs2938392) and
ANKH (rs2454873 and rs379016). All GEE, FBAT and linkage results are provided as an open-access results resource at
http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.