Table 2

Combined OR estimates from case–control mutation screening of nine moderate-risk genes

AnalysisDistinct variantsControl%Case%Adjusted OR*CIp Value
Carrier of truncating or splice junction variant2290.8272.13.311.53 to 7.162.36×10−3
Rare missense substitution analyses
Carrier of rare missense substitution20511410.217613.61.421.09 to 1.848.70×10−3
Carrier of key domain rare missense substitution140655.813610.51.941.41 to 2.675.11×10−5
Carrier of non-key domain rare missense substitution65494.4403.10.740.48 to 1.160.1926
Key domain rMS: MAPP
 rMS<1163393.5584.51.470.95 to 2.260.0818
 rMS≥1177262.3786.02.631.65 to 4.215.32×10−5
Key domain rMS : Align-GVGD
 rMS<C3593544.8876.71.581.09 to 2.270.0146
 rMS≥C3547111.0493.83.621.84 to 7.132.03×10−4
Key domain rMS : CADD
 rMS<2397504.5886.81.661.14 to 2.410.0082
 rMS≥2343151.3483.72.871.57 to 5.266.40×10−4
Key domain rMS : PolyPhen-2
 rMS<0.961373.3554.21.500.96 to 2.340.0752
 rMS≥0.979282.5816.32.491.58 to 3.927.88×10−5
Overlap of missense analysis programs
 One or more89343.0937.22.371.57 to 3.604.56×10−5
 Two or more65181.6705.43.181.85 to 5.462.68×10−5
 Three or more45141.2524.03.271.77 to 6.041.51×10−4
 All four1920.2201.58.611.96 to 37.814.35×10−3
  • *Adjusted for race/ethnicity and study centre.

  • rMS, rare missense substitutions.