Power of the affected‐sib‐pair method for heterogeneous disorders

We have examined the sample sizes required to detect linkage using the affected‐sib‐pair (ASP) method for major psychiatric disorders that are characterized by population prevalences of 1–7%, decreased penetrance, phenocopies, and heterogeneity. In addition, the nature of these illnesses makes large, multigenerational pedigrees difficult to collect. We calculated the sample sizes needed to have 80% power of finding linkage (with a type I error rate of 5%) under dominant and recessive models with incomplete penetrance and allowing for recombination rates of up to 10% between the disease gene and marker gene. We have assumed that the identical‐by‐descent (IBD) status of ASPs is known exactly. For a disease like schizophrenia (1% population prevalence), if 50% of families are linked to a marker locus at 10% recombination, then 60 and 120 pairs are needed under recessive and dominant inheritance, respectively. For a disorder such as major affective disorder (7% population prevalence), the sample size is similar if the inheritance is recessive, but larger (160 pairs) if the inheritance is dominant. We conclude that this method may be a reasonable alternative for psychiatric disorders, especially to confirm that a linkage found in a specific pedigree or population isolate is also present in the general population.