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Table 6 Graded tests

From: Rare key functional domain missense substitutions in MRE11A, RAD50, and NBNcontribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study

Class Adjusted? ln(OR) regression coefficient*(95% CI) Modeled OR at most severe grade(95% CI) Observed OR at most severe grade¥(95% CI)
MRN Key Domain missense, graded$ crude 0.30 (0.055-0.55) 6.16 (1.39-27.3) ¢ 4.31 (0.94-19.7)¢
  adjusted 0.21 (−0.052-0.48) 3.60 (0.73-17.7)¢ 1.80 (0.38-8.44)¢
MRN T + SJV, graded crude 0.14 (−0.088-0.37) 2.34 (0.59-9.34)¢ 2.03 (0.52-7.86)¢
  adjusted 0.15 (−0.091-0.38) 2.41 (0.58-10.0)¢ 2.15 (0.53-8.78)¢
MRN T + SJV + KeyD missense, graded$ crude 0.23 (0.059-0.39) 3.90 (1.42-10.7) ¢ 2.93 (1.08-7.97) ¢
  adjusted 0.18 (0.0011-0.35) 2.89 (1.01-8.30) ¢ 1.97 (0.69-5.62)¢
MRN T + SJV + KeyD missense, graded$ (C65 rMS and in-frame indel removed) crude 0.31 (0.0094-0.62) 3.50 (1.04-11.8) 2.88 (0.79-10.5)
  adjusted 0.33 (0.028-0.64) 3.79 (1.12-12.9) 3.43 (0.91-12.9)
  1. Boldface within the table indicates P <0.05. *From a standard logistic regression of form ln(OR) = a + b(x) in which a = 0, b is the logistic regression OR trend coefficient, and x is, in this case, sequence variant grade. Note that the regression coefficient is significant if its 95% CI excludes 0.00. This is the OR calculated for the most severe grade included in the logistic regression, using the ln(OR) regression coefficient. ¥This is the OR point estimate for carriers of the most severe grade included in the corresponding graded regression model. $The key functional domains are defined in Figure 1. The set of variants includes final exon nonsense and frameshift variants if they also fall in a key functional domain. ¢This is a six-grade regression with the most severe grade consisting of key domain C65 rMS and in-frame indels, truncating variants, and severely damaging splice junction variants. With C65 rMS and the in-frame indel removed, and with no C55 rMS in the data set (Table 4), this is a four-grade regression with the most severe grade consisting of key domain C45 rMS, truncating variants, and severely damaging splice junction variants. OR, odds ratio; CI, confidence interval.