Table 6.
Graded tests
| 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)∞ |
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.