Combined OR estimates from case–control mutation screening of nine moderate-risk genes
| Analysis | Distinct variants | Control | % | Case | % | Adjusted OR* | CI | p Value |
|---|---|---|---|---|---|---|---|---|
| Non-carrier | 148 | 998 | 89.0 | 1094 | 84.4 | Reference | ||
| Carrier of truncating or splice junction variant | 22 | 9 | 0.8 | 27 | 2.1 | 3.31 | 1.53 to 7.16 | 2.36×10−3 |
| Rare missense substitution analyses | ||||||||
| Carrier of rare missense substitution | 205 | 114 | 10.2 | 176 | 13.6 | 1.42 | 1.09 to 1.84 | 8.70×10−3 |
| Carrier of key domain rare missense substitution | 140 | 65 | 5.8 | 136 | 10.5 | 1.94 | 1.41 to 2.67 | 5.11×10−5 |
| Carrier of non-key domain rare missense substitution | 65 | 49 | 4.4 | 40 | 3.1 | 0.74 | 0.48 to 1.16 | 0.1926 |
| Key domain rMS: MAPP | ||||||||
| rMS<11 | 63 | 39 | 3.5 | 58 | 4.5 | 1.47 | 0.95 to 2.26 | 0.0818 |
| rMS≥11 | 77 | 26 | 2.3 | 78 | 6.0 | 2.63 | 1.65 to 4.21 | 5.32×10−5 |
| Key domain rMS : Align-GVGD | ||||||||
| rMS<C35 | 93 | 54 | 4.8 | 87 | 6.7 | 1.58 | 1.09 to 2.27 | 0.0146 |
| rMS≥C35 | 47 | 11 | 1.0 | 49 | 3.8 | 3.62 | 1.84 to 7.13 | 2.03×10−4 |
| Key domain rMS : CADD | ||||||||
| rMS<23 | 97 | 50 | 4.5 | 88 | 6.8 | 1.66 | 1.14 to 2.41 | 0.0082 |
| rMS≥23 | 43 | 15 | 1.3 | 48 | 3.7 | 2.87 | 1.57 to 5.26 | 6.40×10−4 |
| Key domain rMS : PolyPhen-2 | ||||||||
| rMS<0.9 | 61 | 37 | 3.3 | 55 | 4.2 | 1.50 | 0.96 to 2.34 | 0.0752 |
| rMS≥0.9 | 79 | 28 | 2.5 | 81 | 6.3 | 2.49 | 1.58 to 3.92 | 7.88×10−5 |
| Overlap of missense analysis programs | ||||||||
| One or more | 89 | 34 | 3.0 | 93 | 7.2 | 2.37 | 1.57 to 3.60 | 4.56×10−5 |
| Two or more | 65 | 18 | 1.6 | 70 | 5.4 | 3.18 | 1.85 to 5.46 | 2.68×10−5 |
| Three or more | 45 | 14 | 1.2 | 52 | 4.0 | 3.27 | 1.77 to 6.04 | 1.51×10−4 |
| All four | 19 | 2 | 0.2 | 20 | 1.5 | 8.61 | 1.96 to 37.81 | 4.35×10−3 |
| Total | 375 | 1121 | 1297 | |||||
*Adjusted for race/ethnicity and study centre.
rMS, rare missense substitutions.