PT - JOURNAL ARTICLE
AU - Shibata, Kyoko
AU - Ito, Toshikazu
AU - Kitamura, Yutaka
AU - Iwasaki, Naoko
AU - Tanaka, Hiroshi
AU - Kamatani, Naoyuki
TI - Simultaneous Estimation of Haplotype Frequencies and Quantitative Trait Parameters
AID - 10.1534/genetics.104.029751
DP - 2004 Sep 01
TA - Genetics
PG - 525--539
VI - 168
IP - 1
4099 - http://www.genetics.org/content/168/1/525.short
4100 - http://www.genetics.org/content/168/1/525.full
SO - Genetics2004 Sep 01; 168
AB - The analysis of the haplotype-phenotype relationship has become more and more important. We have developed an algorithm, using individual genotypes at linked loci as well as their quantitative phenotypes, to estimate the parameters of the distribution of the phenotypes for subjects with and without a particular haplotype by an expectation-maximization (EM) algorithm. We assumed that the phenotype for a diplotype configuration follows a normal distribution. The algorithm simultaneously calculates the maximum likelihood (L0max) under the null hypothesis (i.e., nonassociation between the haplotype and phenotype), and the maximum likelihood (Lmax) under the alternative hypothesis (i.e., association between the haplotype and phenotype). Then we tested the association between the haplotype and the phenotype using a test statistic, −2 log(L0max/Lmax). The above algorithm along with some extensions for different modes of inheritance was implemented as a computer program, QTLHAPLO. Simulation studies using single-nucleotide polymorphism (SNP) genotypes have clarified that the estimation was very accurate when the linkage disequilibrium between linked loci was rather high. Empirical power using the simulated data was high enough. We applied QTLHAPLO for the analysis of the real data of the genotypes at the calpain 10 gene obtained from diabetic and control subjects in various laboratories.