Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data

J Hum Genet. 2021 Jun;66(6):557-567. doi: 10.1038/s10038-020-00874-x. Epub 2020 Nov 23.

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.

MeSH terms

  • B-Lymphocytes / classification
  • B-Lymphocytes / immunology
  • B-Lymphocytes / ultrastructure
  • B-Lymphocytes / virology
  • Data Mining
  • Female
  • Flow Cytometry
  • Genome-Wide Association Study*
  • Humans
  • Immune System / ultrastructure
  • Immune System / virology*
  • Influenza Vaccines / adverse effects
  • Influenza, Human / blood*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control
  • Lymphocytes / immunology*
  • Lymphocytes / ultrastructure
  • Lymphocytes / virology
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • T-Lymphocytes / classification
  • T-Lymphocytes / immunology
  • T-Lymphocytes / ultrastructure
  • T-Lymphocytes / virology
  • Vaccination / adverse effects

Substances

  • Influenza Vaccines