Abstract
Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data.
Highlights
The human immune system is highly complex [1]
We identified new single-nucleotide polymorphisms (SNPs) related to the individual differences in lymphocyte profiles and their changes after vaccination via a genome-wide association study (GWAS) for these feature statistics
To examine the genetic effects of the lymphocyte profiles, a GWAS was performed on the multidimensional scaling (MDS) coordinate values, and SNPs that were significantly related to these feature statistics were examined
Summary
The human immune system is highly complex [1] It is still unclear what individual differences exist in the phenotype of a healthy person’s immune system. To investigate complex biological phenomena, such as the immune response to vaccination, genome-wide association studies (GWASs) are a powerful approach. They can detect the single-nucleotide polymorphisms (SNPs) that are associated with complex traits [2]. For the immune response to vaccination, several GWAS analyses have been conducted, and in these analyses, the blood cytokine measurement or titer [3, 4] has been used to represent the immune response These previous studies have successfully detected genetic variants associated with the immune response to vaccination. The immunophenotype is very complex and difficult to comprehensively characterize by using the concentrations of single blood metabolites
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