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] |