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Effective Sample Size of Affected Sib Pairs in Case-Control Analyses

Many sibpair collections have been established for linkage mapping studies. These collections can be valuable resources for association studies, but the correlation among siblings must be appropriately allowed for in the analysis to obtain valid tests. We propose an “effective sample size” method to capture the correlation among genotypes of sibs from the same pedigree. This method is based on a theoretical calculation of standard errors and variances of the genotype frequency when siblings are included in the dataset. When the effective sample size method is applied to case-control analysis, where control samples are independent but case samples are collected from the affected-sib-pairs, the confidence interval of odd-ratio can be approximatedly calculated. This calculation is straightforward to carry out and thus simplifies the procedure for including both sibs, from previously collected affected-sib-pair pedigrees, in a case-control analysis. The method extends in studies with mixed sibpairs and singletons for cases and controls. The method is implemented for the scientific community at an online web site.