Scientific Concept of the National Cohort (status ... - Nationale Kohorte

C.2
C.2 Annex: Methods for Statistical Power and Sample Size Calculations
C.2.3 Interaction effects between genetic and non-genetic (“environmen-
N cases tal”) risk factors.
10000
9000
In Sect. A.6.4.3 of the study protocol (main text), figure 6.5 shows the minimal detectable
odds 8000ratio
for gene-environment interaction (power 0.80, at significance level of 0.05), in a
nested 7000 case-control study with N cases of disease, and control:case ratios of 4:1, at fixed
(dominant) main effect odds ratios of 1.2 for the genetic variant, and a main effects odds
6000
ratio of 2.0 for the environmental factor.
5000
figure S6.2 below provides similar estimates, but at a significance level of 10-4 , which may
4000
be more appropriate when larger numbers of interactions are being tested simultaneously.
This 3000 figure confirms that, for statistical interaction effects of moderate magnitude (MDOR
for 2000 interaction around 1.5, a sample size of at least 4,000-5,000 cases of disease will be
required for tests at this significance level. In the National Cohort, cumulative incidences
1000
of this magnitude will be reached only for the most common disease outcomes, including
diabetes 0 and myocardial infarction.
0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5
figure S6.2: Study size (number of incident cases of disease) required to detect minimal odds
ratios [MDOR] of various magnitudes, for gene-environment interaction with power 0.80, at significance
level of 10-4 Allele frequency
RGE 1.2 1.3 1.5 1.7 2 2.5
*assuming ; nested main effects case-control odds ratios study of 1.2 with for genetic 4 controls and 2.0 for per non-genetic case*, assuming risk factor main effects
odds ratios of 1.2 for the alpha=0.0001, genetic and prevalence 2.0 for the of non-genetic risk factor risk factor, 20% plus a prevalence of the
non-genetic risk factor of 0.20.
N cases
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5
Allele frequency
RGE 1.2 1.3 1.5 1.7 2 2.5
*assuming main effects odds ratios of 1.2 for genetic and 2.0 for non-genetic risk factor
alpha=0.0001, prevalence of non-genetic risk factor 20%
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