Table 2.
Two-Locus and Core Haplotypes: HRR and Case-Control Analyses[Note]
| Markers | Haplotype | T(n = 40) | nT(n = 40) | EJM1−(n = 106) | C(n = 128) | HRR (95% CI)a,bT vs. nT | OR (95% CI)bEJM1+ vs. EJM1− | OR (95% CI)bT vs. C |
| rs241441-rs1057141 | C-G | .28 | .25 | .22 | .30 | 1.14 (.40–3.21) | 1.36 (.60–3.12) | .90 (.41–1.96) |
| rs1044244-rs241412 | T-T | .28 | .26 | .15 | .18 | 1.09 (.38–3.08) | 1.47 (.58–3.72) | 1.42 (.58–3.49) |
| rs10751-rs2071556 | T-C | .20 | .13 | .08 | .09 | 1.69 (.48–5.86) | 2.91 (1.04–8.14) |
2.61 (1.00–6.89) |
| rs206787-rs3918149 | T-T | .25 | .07 | .07 | .07 | 4.83 (1.07–24.02) |
4.62 (1.67–12.81) |
4.37 (1.67–11.45) |
| rs620202-rs516535 | G-C | .48 | .35 | .35 | .28 | 1.65 (.63–4.26) | 1.69 (.81–3.51) | 2.27 (1.10–4.71) |
| CA repeat-rs635688 | 6-T | .35 | .13 | .09 | .13 | 3.63 (1.10–11.85) |
5.44 (2.15–13.75) |
3.45 (1.53–7.82) |
| rs2066741-rs206781 | T-T | .55 | .25 | .51 | .45 | 3.67 (1.35–9.94) |
1.24 (.61–2.56) | 1.52 (.75–3.09) |
| rs206777-rs497058 | C-T | .38 | .16 | .25 | .24 | 3.25 (1.05–9.92) |
1.82 (.84–3.94) | 1.92 (.91–4.08) |
| rs1044429-rs2581 | C-T | .38 | .39 | .37 | .29 | .95 (.37–2.47) | 1.03 (.49–2.17) | 1.45 (.694–3.04) |
| rs365066-rs375256 | T-T | .18 | .13 | .21 | .17 | 1.52 (.42–5.42) | .80 (.32–2.01) | 1.06 (.42–2.68) |
| rs620202-rs516535-brd2-rs635688-rs2066741 | G-C-6-T-T | .28 | .10 | .13 | .06 | 3.89 (1.46–1.37) |
9.58 (2.97–30.63) |
6.45 (2.36–17.58) |
Note.— C = EJM1− controls; Hap = haplotype; nT = nontransmitted chromosomes of EJM1+ trios; T = transmitted. A core haplotype of five markers (last row), centered on these associated haplotypes, confers a 4- to 10-fold increased disease risk over other haplotypes. Case-control analyses for this haplotype had an 87%–89% power to detect this association. A longer haplotype (not shown) of 11 markers (rs2071556 to rs497058) that includes promoter SNPs is found in six probands with EJM but is present only in two laboratory controls and in one EJM1− control.
HRR indicates five consecutive haplotypes in or around BRD2 (RING3) (rs206787 to rs497058) in LD with disease; three of these haplotypes are also significantly associated in case-control analysis using one or both sets of external controls.
Statistically significant associations are underlined.