Table 3. Evidence of Association of Previously Reported RANK (TNFRSF11A), RANKL (TNFSF11), and OPG (TNFRSF11B) Variants With CTX (ALSPAC Only, n = 2379).
| CTX | Lumbar spine BMD | Femoral neck BMD | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Locus | RSID | Pos | Gene | PMID | r2 | EA | β* | SE | p Value | β* | SE | p Value | β* | SE | p Value |
| 8q24.12 | rs4355801 | 119993054 | TNFRSF11B | 19079262 & 18455228 | 0.90 | A | 0.02 | 0.030 | 4.81 × 10−1 | –0.07 | 0.009 | 8.09 × 10−17 | –0.06 | 0.008 | 5.48 × 10−12 |
| rs7839059 | 120045723 | TNFRSF11B | 23437003 | 0.42 | A | 0.07 | 0.031 | 2.93 × 10−2 | –0.08 | 0.009 | 1.45 × 10−16 | –0.07 | 0.009 | 4.73 × 10−17 | |
| rs2062375 | 120046973 | TNFRSF11B | 20548944 | 0.97 | C | 0.04 | 0.030 | 1.75 × 10−1 | –0.08 | 0.009 | 2.52 × 10−20 | –0.06 | 0.008 | 3.35 × 10−15 | |
| rs2062377a | 120076601 | TNFRSF11B | 19801982 & 22504420 | 1.00 | A | –0.04 | 0.030 | 1.47 × 10−1 | –0.08 | 0.009 | 2.26 × 10−20 | –0.06 | 0.008 | 2.50 × 10−14 | |
| rs6469792 | 120077552 | TNFRSF11B | 19079262 | 0.74 | C | 0.03 | 0.029 | 3.93 × 10−1 | –0.08 | 0.009 | 3.12 × 10−20 | –0.07 | 0.008 | 2.38 × 10−16 | |
| rs11995824 | 120081881 | TNFRSF11B | 19801982 | 0.79 | G | 0.03 | 0.030 | 3.58 × 10−1 | –0.08 | 0.009 | 5.33 × 10−20 | –0.07 | 0.008 | 1.02 × 10−16 | |
| rs6469804 | 120114010 | TNFRSF11B | 18445777 & 19079262 | 0.88 | A | 0.05 | 0.030 | 1.09 × 10−1 | –0.08 | 0.009 | 5.08 × 10−18 | –0.06 | 0.008 | 1.94 × 10−11 | |
| rs6993813 | 120121419 | TNFRSF11B | 18445777 & 19079262 | 0.69 | C | 0.03 | 0.030 | 3.12 × 10−1 | –0.08 | 0.009 | 1.45 × 10−18 | –0.06 | 0.008 | 6.41 × 10−14 | |
| 13q14.11 | rs9533090a | 41849449 | AKAP11 | 19801982 & 22504420 | 1.00 | T | 0.09 | 0.029 | 3.32 × 10−3 | –0.11 | 0.009 | 1.02 × 10−35 | –0.05 | 0.008 | 9.84 × 10−11 |
| rs9594738 | 41850145 | TNFSF11 | 18445777 & 19079262 | 1.00 | T | 0.09 | 0.029 | 3.30 × 10−3 | –0.11 | 0.009 | 6.46 × 10−35 | –0.05 | 0.008 | 1.27 × 10−10 | |
| rs9533093 | 41859597 | TNFSF11 | 19079262 | 0.23 | T | 0.02 | 0.034 | 5.78 × 10−1 | –0.07 | 0.010 | 1.67 × 10−11 | –0.03 | 0.010 | 5.77 × 10−4 | |
| rs9594759 | 41930593 | TNFSF11 | 18445777 & 19079262 | 0.68 | T | 0.04 | 0.029 | 1.50 × 10−1 | –0.07 | 0.009 | 4.66 × 10−15 | –0.03 | 0.008 | 1.25 × 10−3 | |
| rs1021188a | 42014133 | TNFSF11 | 21124946 & 23437003 | 0.00 | C | 0.14 | 0.038 | 4.12 × 10−4 | –0.03 | 0.011 | 9.51 × 10−3 | –0.02 | 0.010 | 1.71 × 10−2 | |
| 18q21.33 | rs884205a | 58205837 | TNFRSF11A | 19801982 & 22504420 | 1.00 | A | 0.11 | 0.034 | 1.14 × 10−3 | –0.06 | 0.011 | 4.85 × 10−9 | –0.04 | 0.010 | 3.87 × 10−5 |
| rs3018362 | 58233073 | TNFRSF11A | 19079262 | 0.68 | A | 0.07 | 0.031 | 3.78 × 10−2 | –0.04 | 0.009 | 7.15 × 10−6 | –0.03 | 0.009 | 7.30 × 10−5 | |
Pos = position in the genome based on hg18; Gene = closest gene; PMID = accession number of the publication in Pubmed, which described the association with BMD; r2 = the pairwise LD estimate in CEU populations between the SNP in bold and all other SNPs in that locus; EA = effect allele; β* = effect size; SE = standard error of β*.
Effect estimates expressed as adjusted SD per copy of the effect allele (EA). Note: rs9533090 is found upstream of TNFSF11 but is closest to AKAP11. Data are also shown for lumbar spine and femoral neck BMD associations from the GEFOS publicly released data set (rs7839059 and rs1021188 were identified from a GWAS meta‐analysis based on BMDC as opposed to areal BMD).
Denotes the variants that were used to generate allele scores (ie, independent signals [rs1021188 was also included by virtue of genome‐wide significant association with BMDc]).