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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.