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Sample size requirements to detect the effect of a group of genetic variants in case-control studies.

Moonesinghe R, Yang Q, Khoury MJ - Emerg Themes Epidemiol (2008)

Bottom Line: For a range of reasonable numbers of genetic variants, the sample size requirements for the test statistic proposed here are generally not larger than those needed for assessing marginal effects of individual variants and actually decline with increasing number of genetic variants in many situations considered in the group.When a significant effect of the group of genetic variants is detected, subsequent multiple tests could be conducted to detect which individual genetic variants and their combinations are associated with disease risk.When testing for an effect size in a group of genetic variants, one can use our global test described in this paper, because the sample size required to detect an effect size in the group is comparatively small.

View Article: PubMed Central - HTML - PubMed

Affiliation: Office of Minority Health and Health Disparities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. RMoonesinghe@cdc.gov

ABSTRACT

Background: Because common diseases are caused by complex interactions among many genetic variants along with environmental risk factors, very large sample sizes are usually needed to detect such effects in case-control studies. Nevertheless, many genetic variants act in well defined biologic systems or metabolic pathways. Therefore, a reasonable first step may be to detect the effect of a group of genetic variants before assessing specific variants.

Methods: We present a simple method for determining approximate sample sizes required to detect the average joint effect of a group of genetic variants in a case-control study for multiplicative models.

Results: For a range of reasonable numbers of genetic variants, the sample size requirements for the test statistic proposed here are generally not larger than those needed for assessing marginal effects of individual variants and actually decline with increasing number of genetic variants in many situations considered in the group.

Conclusion: When a significant effect of the group of genetic variants is detected, subsequent multiple tests could be conducted to detect which individual genetic variants and their combinations are associated with disease risk. When testing for an effect size in a group of genetic variants, one can use our global test described in this paper, because the sample size required to detect an effect size in the group is comparatively small. Our method could be viewed as a screening tool for assessing groups of genetic variants involved in pathogenesis and etiology of common complex human diseases.

No MeSH data available.


Related in: MedlinePlus

Sample size for varying values of K and G (R = 1.25). Approximate sample sizes required to achieve 80% power at 5% significance level in detecting the difference in mean exposure between cases and controls due to a hypothetical group of k identical genetic variants with a risk ratio of 1.25.
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Figure 1: Sample size for varying values of K and G (R = 1.25). Approximate sample sizes required to achieve 80% power at 5% significance level in detecting the difference in mean exposure between cases and controls due to a hypothetical group of k identical genetic variants with a risk ratio of 1.25.

Mentions: We calculated the sample size required to detect a hypothetical group of k identical genetic variants (all loci are equivalent having equal effects and are independent). Figures 1, 2, and 3 give the approximate sample size (number of cases in 1:1 design) required to achieve 80% power at 5% significance level for detecting mean exposure due to a hypothetical group of k identical genetic variants when the prevalence varies from 0.1 to 0.9 and k varies from 1 to 10. Figure 1 corresponds to a risk ratio of 1.25, while figures 2 and 3 assume risk ratios of 1.5 and 2.0, respectively.


Sample size requirements to detect the effect of a group of genetic variants in case-control studies.

Moonesinghe R, Yang Q, Khoury MJ - Emerg Themes Epidemiol (2008)

Sample size for varying values of K and G (R = 1.25). Approximate sample sizes required to achieve 80% power at 5% significance level in detecting the difference in mean exposure between cases and controls due to a hypothetical group of k identical genetic variants with a risk ratio of 1.25.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651869&req=5

Figure 1: Sample size for varying values of K and G (R = 1.25). Approximate sample sizes required to achieve 80% power at 5% significance level in detecting the difference in mean exposure between cases and controls due to a hypothetical group of k identical genetic variants with a risk ratio of 1.25.
Mentions: We calculated the sample size required to detect a hypothetical group of k identical genetic variants (all loci are equivalent having equal effects and are independent). Figures 1, 2, and 3 give the approximate sample size (number of cases in 1:1 design) required to achieve 80% power at 5% significance level for detecting mean exposure due to a hypothetical group of k identical genetic variants when the prevalence varies from 0.1 to 0.9 and k varies from 1 to 10. Figure 1 corresponds to a risk ratio of 1.25, while figures 2 and 3 assume risk ratios of 1.5 and 2.0, respectively.

Bottom Line: For a range of reasonable numbers of genetic variants, the sample size requirements for the test statistic proposed here are generally not larger than those needed for assessing marginal effects of individual variants and actually decline with increasing number of genetic variants in many situations considered in the group.When a significant effect of the group of genetic variants is detected, subsequent multiple tests could be conducted to detect which individual genetic variants and their combinations are associated with disease risk.When testing for an effect size in a group of genetic variants, one can use our global test described in this paper, because the sample size required to detect an effect size in the group is comparatively small.

View Article: PubMed Central - HTML - PubMed

Affiliation: Office of Minority Health and Health Disparities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. RMoonesinghe@cdc.gov

ABSTRACT

Background: Because common diseases are caused by complex interactions among many genetic variants along with environmental risk factors, very large sample sizes are usually needed to detect such effects in case-control studies. Nevertheless, many genetic variants act in well defined biologic systems or metabolic pathways. Therefore, a reasonable first step may be to detect the effect of a group of genetic variants before assessing specific variants.

Methods: We present a simple method for determining approximate sample sizes required to detect the average joint effect of a group of genetic variants in a case-control study for multiplicative models.

Results: For a range of reasonable numbers of genetic variants, the sample size requirements for the test statistic proposed here are generally not larger than those needed for assessing marginal effects of individual variants and actually decline with increasing number of genetic variants in many situations considered in the group.

Conclusion: When a significant effect of the group of genetic variants is detected, subsequent multiple tests could be conducted to detect which individual genetic variants and their combinations are associated with disease risk. When testing for an effect size in a group of genetic variants, one can use our global test described in this paper, because the sample size required to detect an effect size in the group is comparatively small. Our method could be viewed as a screening tool for assessing groups of genetic variants involved in pathogenesis and etiology of common complex human diseases.

No MeSH data available.


Related in: MedlinePlus