"Forward genetics" as a method to maximize power and cost-efficiency in studies of human complex traits.
There is increasing interest in methods to disentangle the relationship between genotype and (endo)phenotypes in human complex traits. We present a population-based method of increasing the power and cost-efficiency of studies by selecting random individuals with a particular genotype and then assessing the accompanying quantitative phenotypes. Using statistical derivations, power- and cost graphs we show that such a "forward genetics" approach can lead to a marked reduction in sample size and costs. This approach is particularly apt for implementing in epidemiological studies for which DNA is already available but the phenotyping costs are high.
Boks
M P M
MP
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, Utrecht, The Netherlands. mboks@umcutrecht.nl
Derks
E M
EM
Dolan
C V
CV
Kahn
R S
RS
Ophoff
R A
RA
D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D005828:Genetics, Population / Q000191:economics* / Q000379:methods* / Q000706:statistics & numerical data*; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D019655:Quantitative Trait, Heritable