Creating an Immune Inventory
An EHR-derived phenotypic disease catalog has allowed researchers to replicate four decades of work on human leukocyte antigen
Roisin McGuigan |
Autoimmune diseases are as varied as they are poorly understood, with the potential to affect almost all organs and tissues of the body. There are around 80 recognized autoimmune diseases, and many have been linked to human leukocyte antigen (HLA) – a gene complex that codes for major histocompatibility complex (MHC) proteins, and plays a crucial role in the immune system.
Over the years, many studies have linked HLA genes to a variety of specific diseases – but one team decided to take the wider view. To create a catalog of diseases associated with HLA, they used data from 13,835 people, screening for the presence of almost 1,400 phenotypes using patient samples and electronic health records (EHRs). The resulting phenome-wide association study (PHeWAS) essentially offers a reverse perspective to a GWAS by analyzing many phenotypes compared to a single genetic variant. The results are freely available online for researchers to access and use (1).
“Through this bioinformatics study we have essentially replicated forty years’ worth of research on this topic, in one fell swoop. The strong associations we found, and the resources at our disposal, allowed us to do this both quickly and efficiently,” says Jason Karnes, Assistant Professor at the University of Arizona College of Pharmacy, and co-first author of the paper.
The research team found strong associations between HLA genes and over 100 diseases, many of them autoimmune. There were also associations with other diseases, such as cervical cancer, but the researchers expected more. “We had a hypothesis that maybe we’d find that some HLA variants protected against cancers, or against infectious disease – diseases outside the autoimmune space. But we didn’t find too many surprising results,” adds Joshua Denny, senior author of the study and professor of Biomedical Informatics and Medicine at Vanderbilt.
But in many ways, their catalog is just the beginning. “Our hope is that other researchers will be able to use our database as a resource to aid their own research. People will download this data and do new things that we haven’t even thought of, which is fantastic,” says Denny. The team also have their eyes on other areas that could be studied using this approach. “It doesn’t stop with HLA – there’s a lot of data that we can create using a similar approach, but looking at different areas of the genome,” says Karnes.
- 1JC Denny et al., “Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data”, Nat Biotechnol, 31, 1102–1110 (2013). PMID: 24270849.