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Power of the affected‐sib‐pair method for heterogeneous disorders
Author(s) -
Goldin Lynn R.,
Gershon Elliot S.,
Borecki I. B.
Publication year - 1988
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.1370050104
Subject(s) - penetrance , pedigree chart , genetics , phenocopy , population , locus (genetics) , genetic linkage , major gene , biology , linkage (software) , genetic heterogeneity , identity by descent , gene , allele , medicine , haplotype , phenotype , environmental health
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.