Sample size calculations for population- and family-based case-control association studies on marker genotypes.
Most previous sample size calculations for case-control studies to detect genetic associations with disease assumed that the disease gene locus is known, whereas, in fact, markers are used. We calculated sample sizes for unmatched case-control and sibling case-control studies to detect an association between a biallelic marker and a disease governed by a putative biallelic disease locus. Required sample sizes increase with increasing discrepancy between the marker and disease allele frequencies, and with less-than-maximal linkage disequilibrium between the marker and disease alleles. Qualitatively similar results were found for studies of parent offspring triads based on the transmission disequilibrium test (Abel and Müller-Myhsok, 1998, Am. J. Hum. Genet. 63:664-667; Tu and Whittemore, 1999, Am. J. Hum. Genet. 64:641-649). We also studied other factors affecting required sample size, including attributable risk for the disease allele, inheritance mechanism, disease prevalence, and for sibling case-control designs, extragenetic familial aggregation of disease and recombination. The large sample-size requirements represent a formidable challenge to studies of this type.
Pfeiffer
Ruth M
RM
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-7244, USA. pfeiffer@mail.nih.gov
Gail
Mitchell H
MH
D000483:Alleles; D016022:Case-Control Studies; D015340:Epidemiologic Research Design; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D015233:Models, Statistical; D018401:Sample Size
D005819:Genetic Markers