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We compared the relative detection power of random, case-control, and case-parent control (TDT) study designs by computer simulation of five parameters: Mode of inheritance (MOl), magnitude of genetic effect (r ), disease susceptibility allele frequency in the founder population (PI)' population age (t ), and the genetic distance ((} ) between disease susceptibility locus ( D ), and marker locus (M). Our results show that none of the three study designs can be claimed to be the most powerful (requiring the smallest sample size) constantly under every different genetic context (parameter combination). Our analysis indicates that both case-parent control and case-control designs have more power than the random sampling design in most genetic contexts. But the relative power between case-parent and case control depends on the specific parameter combinations. Random sampling has more power than case-parent control (although less power than case-control design) under some high genetic effect (r ) and initial allele frequency (PI) combinations. All the three study designs show the most power under additive models of inheritance and least power under recessive mode of inheritance.

DETECTION POWER OF RANDOM, CASE-CONTROL, AND CASE-PARENT CONTROL DESIGNS FOR ASSOCIATION TESTS AND GENETIC MAPPING OF COMPLEX TRAITS