We consider a binary trait and focus on detecting association with disease at a single locus with two alleles \(A\) and \(a\). The likelihood ratio test is based on a binomial mixture model of \(J\) components (\(J \ge 2\)) for diseased cases: $$P_{\eta}(X_D=g)=\sum_{j=1}^J \alpha_j B_2(g, \theta_j), \; g=0, 1, 2, \; J \geq 2, \; \sum_{j=1}^J \alpha_j=1, \; \theta_j, \alpha_j \in (0, 1),$$ where \(\eta=(\eta_j)_{j \leq J}, \eta_j=(\theta_j, \alpha_j)^T, j=1, \ldots, J\), \(B_2(g, \theta_j)\) is the probability mass function for a binomial distribution \(X \sim Bin(2, \theta_j)\), and \(\theta_i=\theta_j\) if and only if \(i=j\). \(\theta_j\) is the probability of having the allele of interest on one chromosome for a subgroup of case \(j\). In particular, \(J\) is likely to be quite large for many of the complex disease with genetic heterogeneity. Note that the LRT-H can be applied to association studies without the need to know the exact value of \(J\) while allowing \(J \ge 2\).
gLRTH_A(n0, n1, n2, m0, m1, m2)AA genotype frequency in case
Aa genotype frequency in case
aa genotype frequency in case
AA genotype frequency in control
Aa genotype frequency in control
aa genotype frequency in control
The test statistic and asymptotic p-value for the likelihood ratio test for GWAS under genetic heterogeneity
Qian M., Shao Y. (2013) A Likelihood Ratio Test for Genome-Wide Association under Genetic Heterogeneity. Annals of Human Genetics, 77(2): 174-182.
# NOT RUN {
gLRTH_A(n0=2940, n1=738, n2=53, m0=3601, m1=1173, m2=117)
# }
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