Combining identity by descent and association in genetic case-control studies.
BACKGROUND
In human case-control association studies, one of the chi-square tests typically carried out is based on a 2 x 3 table of genotypes (homogeneity of three genotype frequencies in case and control individuals). We formulate the two degrees of freedom associated with a given genotype distribution in terms of two biologically relevant parameters, (1) the probability F that an individual's two alleles are identical by descent (IBD) and (2) the frequency p of one of the alleles.


RESULTS
Imposing the restriction, F > or = 0, makes some of the genotype frequencies invalid thereby reducing noise. We propose a new statistical association test, the FP test, by focusing on allele frequency differences between case and control individuals while allowing for suitable IBD probabilities. Power calculations show that (1) the practice of generally carrying out two association tests (allele and genotype test) has an increased type I error and (2) our test is more powerful than conventional genotype and allele tests under recessive trait inheritance, and at least as powerful as these conventional tests under dominant inheritance.


CONCLUSIONS
For dominant and recessive modes of inheritance, any apparent power gain by an allele test when carried out in conjunction with a genotype test tends to be purchased entirely by an increased rate of false positive results due to omission of a multiple testing correction. As an alternative to these two standard association tests, our FP test represents a convenient and more powerful alternative.
Zhang
Qingrun
Q
Beijing Institute of Genomics, Chinese Academy of Sciences, No. 7 Bei Tu Cheng West Road, Beijing 100029, PR China. zhangqr@big.ac.cn
Wang
Shuang
S
Ott
Jurg
J
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005787:Gene Frequency; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D005828:Genetics, Population / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D010375:Pedigree; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide; D012107:Research Design / Q000706:statistics & numerical data*