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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.