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Table 2 Examples of genome-wide-association studies of osteoporosis and related traitsa

From: Genome-wide approaches for identifying genetic risk factors for osteoporosis

Genotyping Total markers Significant markers Discovery participants Replication participants Phenotype P-value Candidate gene/
related pathwayb
Refs
Affymetrix 500K array set 342,854 SNPs. HWE P ≥ 0.0001; MAF ≥5% rs9630182, rs2036417, rs7125774; rs8057551, rs8061992, rs7199138 495 females and 488 males, unrelated 2,557 phenotyped white individuals from 750 families Femoral neck BMD 3.98 × 10-7 to
6.74 × 10-3
IL21R and PTH
/PTH pathway
[52]
Affymetrix 500K array set 281,533 SNPs. Genotypic call rates ≥90%; HWE P ≥ 0.001; MAF ≥5% rs13182402 700 elderly Chinese Han 906 Chinese, 4,054 US Midwest Caucasians, 2,953 US Framingham samples BMD; low-trauma osteoporotic fractures 2.08 × 10-9 to 6.39 × 10-6 ALDH7A1 [40]
Infinium assay Human 610-quad chip 564,214 SNPs. Genotypic call rates ≥95%; HWE P ≥ 0.0001; MAF ≥1% rs2273061 800 unrelated Hong Kong Chinese females 720 Hong Kong and 17,378 of European or Asian descent BMD 5.27 × 10-8 to 3.47 × 10-5 JAG1; Wnt and Notch pathways [46]
High-density oligonucleotide arrays 224,507 SNPs. Genotypic call rates ≥90%; HWE P ≥ 10-6 rs7605378 1,747 (190 cases and 1,557 controls) in Japan 5,206 (2,092 cases, 3,114 controls) in Japanese   1.51 × 10-8 FONG [45]
Affymetrix genome-wide human SNP array 6.0 689,368 SNPs. HWE P ≥ 0.01; MAF ≥1% rs17743190, rs3857454, rs3907327, rs17799762, rs17799805, rs1385530, rs17799462, rs3857453, rs3857449, rs10484943, rs196670, rs16890720 1,627 Han adults 1,728 from Midwestern US (Kansas City, MO and Omaha, NE) Spine bone size 6.2 × 10-5 to 1.8 × 10-6 HMGN3 [50]
Affymetrix GeneChip human mapping SNP 6.0 array 194 CNVs CNP267 1,627 Chinese Han 2,286 unrelated US Caucasians Hip bone size 4.73 × 10-3 and 5.66 × 10-3 FHL2 [30]
Meta-analysis 1,200 SNPs 467 SNPs 19,195 Northern Europeans   Femoral neck and lumbar spine BMD <5 × 10-8 SPTBN1, CTNNB1, MEPE, STARD3NL, FLJ42280; ARHGAP1, DCDC5, SOX6, FOXL1, HDAC5 ESR1, SP7, and others; Wnt and MAPK pathways [31]
Meta-analysis   96 SNPs 32,961 of European and East Asian ancestry Replication in 50,933 individuals Lumbar spine and femoral neck BMD <5 × 10-8 FAM210A, SLC25A13, LRP5, MEPE, SPTBN1, DKK1; RANK-RANKL-OPG and Wnt pathways [33]
  1. aAbout 20 genes have been detected in multiple GWASs, including ARHGAP1 [31, 32], C6orf97 [29, 32], CLCN7 [25, 43], CTNNB1 [31, 53], DCDC5 [31, 53], ESR1 [29, 31, 32, 48, 53, 57], FLJ42280 [31, 53, 55], FOXL1 [31, 53], GPR177 [31, 53, 54], HDAC5 [31, 53], LRP4 [31, 32, 56, 57], LRP5 [31, 33, 53], MEPE [31, 33, 53], PTH [43, 52], STARD3NL [31, 53], SOST [53, 56], SOX6 [31, 41, 51, 53], SPTBN1 [31, 33, 57], TNFSF11 [55, 56], TNFRSF11A [31, 37, 55, 56], TNFSF11B [31, 53, 56, 57], and ZBTB40 [31, 53]. bFor gene abbreviations and explanations of pathways, see Table 5.