A generalized model for combining dependent SNP-level summary statistics and its extensions to statistics of other levels.

Here I propose a fundamentally new flexible model to reveal the association between a trait and a set of genetic variants in a genomic region/gene. This model was developed for the situation when original individual-level phenotype and genotype data are not available, but the researcher possesses the results of statistical analyses conducted on these data (namely, SNP-level summary Z score statistics and SNP-by-SNP correlations). The new model was analytically derived from the classical multiple linear regression model applied for the region-based association analysis of individual-level phenotype and genotype data by using the linear compression of data, where the SNP-by-SNP correlations are among the explanatory variables, and the summary Z score statistics are categorized as the response variables. I analytically show that the regional association analysis methods developed within the framework of the classical multiple linear regression model with additive effects of genetic variants can be reformulated in terms of the new model without the loss of information. The results obtained from the regional association analysis utilizing the classical model and those derived using the proposed model are identical when SNP-by-SNP correlations and SNP-level statistics are estimated from the same genetic data.