Kernel-based association test.
Association mapping (i.e., linkage disequilibrium mapping) is a powerful tool for positional cloning of disease genes. We propose a kernel-based association test (KBAT), which is a composite function of "P-values of single-locus association tests" and "kernel weights related to intermarker distances and/or linkage disequilibria." The KBAT is a general form of some current test statistics. This method can be applied to the study of candidate genes and can scan each chromosome using a moving average procedure. We evaluated the performance of the KBAT through simulation studies that considered evolutionary parameters, disease models, sample sizes, kernel functions, test statistics, window attributes, empirical P-value estimations, and genetic/physical maps. The results showed that the KBAT had a well-controlled false positive rate and high power compared to existing methods. In addition, the KBAT was also applied to analyze a genomewide data set from the Collaborative Study on the Genetics of Alcoholism. Important genes associated with alcoholism dependence were identified. In summary, the merits of the KBAT are multifold: the KBAT is robust against the inclusion of nuisance markers, is invariant to the map scale, and accommodates different types of genomic data, study designs, and study purposes. The proposed methods are packaged in the user-friendly software, KBAT, available at http://www.stat.sinica.edu.tw/hsinchou/genetics/association/KBAT.htm.
Institute of Statistical Science, Academia Sinica, 128 Academia Rd., Sec. 2, Nankang, Taipei, Taiwan 115. hsinchou@stat.sinica.edu.tw
Hsin-Chou
HC
Yang
Hsin-Yi
HY
Hsieh
Cathy S J
CS
Fann
D000437:Alcoholism / Q000235:genetics; D005075:Biological Evolution; D001699:Biometry; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D003001:Cloning, Molecular; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020161:Physical Chromosome Mapping / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D018401:Sample Size; D012984:Software