Related Experiment Video

Updated: May 14, 2026

Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation
08:07

Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation

Published on: September 6, 2017

A PheWAS approach in studying HLA-DRB1*1501

S J Hebbring1, S J Schrodi, Z Ye

  • 1Department of Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA. hebbring.scott@mcrf.mfldclin.edu

Genes and Immunity
|February 9, 2013
PubMed

Insights

The HLA-DRB1*1501 genetic variant, linked to multiple sclerosis (MS), was also strongly associated with alcohol-induced liver cirrhosis in a large-scale phenome-wide association study (PheWAS). This research highlights novel associations and validates the PheWAS approach.

Area of Science:

  • Genetics
  • Immunology
  • Computational Biology

Background:

  • The Human Leukocyte Antigen (HLA) complex plays a crucial role in immune responses.
  • Genetic variations within the HLA-DRB1 gene are implicated in various autoimmune diseases.
  • The HLA-DRB1*1501 haplotype is a known risk factor for multiple sclerosis (MS).

Purpose of the Study:

  • To investigate the association of the rs3135388 genotype, which tags the HLA-DRB1*1501 haplotype, with a wide range of health phenotypes.
  • To validate the utility and feasibility of the phenome-wide association study (PheWAS) approach using external data.
  • To explore potential novel associations of the HLA-DRB1*1501 locus beyond known autoimmune links.

Main Methods:

  • A phenome-wide association study (PheWAS) was conducted using electronic health records from 4235 individuals.
  • The study analyzed the association between the rs3135388 genotype (tagging HLA-DRB1*1501) and 4841 distinct phenotypes.
  • Statistical analyses were performed to identify significant genotype-phenotype associations, including those for multiple sclerosis and other conditions.

Main Results:

  • The expected association between HLA-DRB1*1501 and multiple sclerosis (ICD9 340) was confirmed (P=0.023).
  • The strongest association identified was between HLA-DRB1*1501 and alcohol-induced cirrhosis of the liver (ICD9 571.2, P=0.00011).
  • Additional significant associations were found with erythematous conditions (ICD9 695, P=0.0054) and benign respiratory neoplasms (ICD9 212, P=0.042).

Conclusions:

  • The study successfully validated the PheWAS approach as a powerful tool for genetic discovery.
  • The findings reveal a significant association between the HLA-DRB1*1501 locus and alcohol-induced liver cirrhosis, suggesting a broader role beyond autoimmunity.
  • This research underscores the complex genetic underpinnings of the HLA-DRB1*1501 locus and its potential involvement in diverse pathologies.

More Related Videos

Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix10:37

Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix

Published on: October 20, 2021

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis09:32

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Published on: October 15, 2021

Related Concept Videos

Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...