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

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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% 280
Table S6.7a: Minimum detectable odds ratios [MDOR] for gene-environment interaction (statistical (statistical power power of 0.80; of 0.80; dominant dominant effects effects model model for for the the genetic variant), by by allele frequency, by by non-genetic risk risk factor factor prevalence, and and by by significance significance level; level; nested nested case-control case-control study study with with 2 controls 2 controls per per case. case. Minimum detectable OR for gene-environment interaction (2 controls) 10,000 cases 5000 cases 4000 cases 3000 cases 2500 cases 2000 cases 1500 cases 1000 cases 700 cases 500 cases 400 cases 300 cases 200 cases 150 cases Non-genetic factor prevalence Genotype prevalence C.2 Annex: Methods for Statistical Power and Sample Size Calculations Critical p-value 0.05 0.05 0.05 13.5 9.8 6.7 5.4 4.6 3.8 3.1 2.6 2.3 2.1 2.0 1.8 1.7 1.5 0.05 0.05 10 -4 51.2 22.3 14.8 11.3 8.0 6.0 4.5 3.8 3.3 3.0 2.7 2.4 1.9 0.1 0.05 0.05 8.8 6.7 4.8 4.0 3.5 2.9 2.5 2.1 2.0 1.8 1.7 1.6 1.5 1.4 0.1 0.05 10 -4 47.2 24.8 13.2 9.4 7.5 5.6 4.3 3.4 2.9 2.6 2.4 2.2 2.0 1.7 0.25 0.05 0.05 7.4 5.6 4.1 3.4 3.0 2.6 2.2 1.9 1.8 1.7 1.6 1.5 1.4 1.3 0.25 0.05 10 -4 43.3 22.0 11.4 8.0 6.4 4.8 3.7 2.9 2.5 2.3 2.2 2.0 1.8 1.5 0.5 0.05 0.05 16.6 10.5 6.4 4.9 4.1 3.3 2.7 2.2 1.9 1.9 1.8 1.6 1.6 1.4 0.5 0.05 10 -4 36.1 18.9 12.8 8.0 5.5 3.9 3.2 2.9 2.6 2.3 2.1 1.7 0.05 0.1 0.05 8.0 6.2 4.6 3.8 3.3 2.8 2.4 2.1 1.9 1.8 1.7 1.6 1.5 1.4 0.05 0.1 10 -4 34.9 20.2 11.6 8.5 6.9 5.2 4.1 3.3 2.8 2.6 2.4 2.1 2.0 1.6 0.1 0.1 0.05 5.5 4.4 3.4 2.9 2.6 2.3 2.0 1.8 1.7 1.6 1.5 1.4 1.4 1.3 0.1 0.1 10 -4 18.2 11.9 7.5 5.8 4.9 3.9 3.1 2.6 2.3 2.1 2.0 1.8 1.7 1.5 0.25 0.1 0.05 4.7 3.8 3.0 2.6 2.3 2.0 1.8 1.6 1.5 1.5 1.4 1.4 1.3 1.2 0.25 0.1 10 -4 16.6 10.4 6.4 4.9 4.1 3.3 2.7 2.3 2.0 1.9 1.8 1.7 1.6 1.4 0.5 0.1 0.05 8.4 5.9 4.1 3.3 2.9 2.4 2.1 1.8 1.7 1.6 1.5 1.4 1.4 1.3 0.5 0.1 10 -4 50.6 15.3 9.2 6.9 4.8 3.6 2.8 2.4 2.2 2.1 1.9 1.7 1.5 0.05 0.2 0.05 5.8 4.6 3.5 3.0 2.7 2.4 2.1 1.8 1.7 1.6 1.5 1.5 1.4 1.3 0.05 0.2 10 -4 20.2 12.9 8.0 6.1 5.1 4.0 3.2 2.7 2.4 2.2 2.0 1.9 1.7 1.5 0.1 0.2 0.05 4.1 3.4 2.8 2.4 2.2 2.0 1.8 1.6 1.5 1.4 1.4 1.3 1.3 1.2 0.1 0.2 10 -4 11.8 8.1 5.5 4.3 3.7 3.1 2.6 2.2 2.0 1.8 1.7 1.6 1.5 1.4 0.25 0.2 0.05 3.6 3.0 2.5 2.2 2.0 1.8 1.6 1.5 1.4 1.4 1.3 1.3 1.2 1.17 0.25 0.2 10 -4 11.6 7.4 4.7 3.8 3.2 2.7 2.3 2.0 1.8 1.7 1.6 1.5 1.4 1.3 0.5 0.2 0.05 6.4 4.5 3.2 2.7 2.4 2.1 1.8 1.6 1.5 1.5 1.4 1.3 1.3 1.2 0.5 0.2 10 -4 14.0 7.1 5.2 3.8 2.9 2.4 2.1 1.9 1.8 1.7 1.6 1.4 * assuming main effects odds ratios of 1.2 for genetic and 2.0 for non-genetic risk factor ** highlighted are the combinations where MDOR is 1.5 or smaller 281 C.2
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The National Cohort A prospective e
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Applicants Applicants Applicants Cl
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Applicants IV
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Executive Summary 2. The National C
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Executive Summary 3. Scientific aim
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Executive Summary essary to address
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Executive Summary 7. Examples for s
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Contents A.2.4 major areas of expos
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Contents A.3.8.2 Social security da
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Contents A.6.4.2 Minimally detectab
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Abbreviations C.2 mEThOdS fOr STATI
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Abbreviations DXA Dual-energy x-ray
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Abbreviations CHS Cardiovascular He
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A.1 A.1 Introduction and overview a
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