Background Osteoporosis is seen as a low bone mass and compromised bone structure, heritable traits that contribute to fracture risk. 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 729607-74-3 manufacture 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. Conclusion The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate Bglap previously suggested candidate genes for osteoporosis. Introduction Osteoporosis is a skeletal disorder characterized by compromised bone strength leading to an increased risk of fracture [1]. In the United States alone, there are over 1.5 million fractures each year, including 280,000 hip fractures and 500,000 vertebral fractures. According to the recent U.S. Surgeon General’s Report on Skeletal Health, fractures remain a large and growing public health concern [2]. Presently, the gold standard for assessment of fracture risk is measurement of bone mineral density (BMD, g/cm2) by dual-energy X-ray absorptiometry (DXA). Whereas low BMD is among the strongest risk elements for fracture [3,4], a genuine amount of medical research possess shown that additional measurements, such as for example quantitative ultrasound (QUS) and bone tissue geometry, are essential for fracture osteoporosis and prediction treatment monitoring [5-7]. Thus, QUS from the calcaneus can be connected with hip fracture, 3rd party of BMD [8 mainly,9]. An evergrowing body of 729607-74-3 manufacture proof lately shows that femoral geometry also contributes significantly to hip fracture risk [10,11]. BMD, QUS, and femoral bone tissue geometry are around distributed, complex traits. An abundance of studies possess documented BMD to become under strong hereditary control with 50C70% heritability [12,13]. Likewise, QUS [8,14,15] and hip geometry [16-19] are most likely controlled by additive hereditary factors. Nevertheless, despite many years of study in neuro-scientific osteoporosis genetics, improvement to date has been modest in successfully identifying major genes determining BMD, QUS, and bone geometry in the general population. The numbers of quantitative trait loci (QTLs) and genes linked and/or associated with osteoporosis-related phenotypes continue to expand and the list has become considerably more detailed and complex. More than 20 genome linkage scans to date have revealed multiple QTLs covering all chromosomes but the Y chromosome [20]. Moreover, the results from one study have inconsistently been replicated in other samples. To overcome these obstacles, a collaborative meta-analysis of 9 genome-wide linkage 729607-74-3 manufacture searches of BMD was recently conducted, including data from 11,842 subjects, members of 3,045 families [13]. The meta-analysis suggested a number of specific QTLs to be pursued further (1p13.3-q23.3 and 1q32-q42.3, 3p25.3-p22.1, 11p12-q13.3, 12q24.31-qter, and 18p11-q12.3). An additional 729607-74-3 manufacture factor that adds to the complexity of finding genes for osteoporosis-related traits is the notion (including our own [21,22]) that QTLs for bone density and 729607-74-3 manufacture geometry [23].