Genetic Variants on Chromosome 6 Reflect Different Immune Responses To Infections

Christian Hammer, PhD École Polytechnique Fédérale de Lausanne Swiss Institute of Bioinformatics Lausanne, Switzerland Clinical Neuroscience Max Planck Institute of Experimental Medicine Göttingen, Germany

Dr. Hammer

MedicalResearch.com Interview with:
Christian Hammer, PhD
École Polytechnique
Fédérale de Lausanne Swiss Institute of Bioinformatics
Lausanne, Switzerland
Clinical Neuroscience
Max Planck Institute of Experimental Medicine
Göttingen, Germany

Medical Research: What is the background for this study? What are the main findings?

Dr. Hammer: The immune response after viral infection or vaccination varies considerably from person to person, which is important because these differences can account for clinical outcome or vaccine effectiveness. It has been shown before that part of this variability is heritable, indicating the possibility that differences in our genes might be involved. To test this, we performed a genome-wide association study in more than 2,300 individuals, using high-performance computing to analyze whether differences in the abundance of antibodies against 14 common viruses are caused by variable sites in our genome. We looked at about 6 million of these variants and found that a region on chromosome 6 that harbors many genes involved in immune regulation showed highly significant associations with immune response to influenza A virus, Epstein-Barr virus (EBV), JC polyomavirus, and Merkel Cell polyomavirus. The genetic variants result in structural differences in proteins whose job it is to present fragments of pathogens that have been taken up by cells to the immune system. Interestingly, a given variant can lead to an increased immune response to one virus, e.g. influenza A, and at the same time to a decreased immune response to another, e.g. EBV, which is likely due to an altered ability of the protein to bind and present specific viruses, depending on the genetic background.

Medical Research: What should clinicians and patients take away from your report?

Dr. Hammer: Although precision medicine is still in its infancy, studies like ours contribute to the vast pool of knowledge that will be needed in the future to inform personalized clinical decision making. Tailored drug treatment or vaccination plans are examples for its potential to improve healthcare.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Hammer: In genomics, large cohorts are essential for the identification and validation of the effect of common genetic variants on complex traits. We are therefore trying to collect more data to substantiate our results and identify novel associations. In parallel, it will of course be important to investigate our findings, which are based on statistical analyses, in the lab to obtain a deeper understanding of their functional consequences.

Citation:

Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses.

Hammer C1, Begemann M2, McLaren PJ3, Bartha I3, Michel A4, Klose B5, Schmitt C5, Waterboer T4, Pawlita M4, Schulz TF5, Ehrenreich H6, Fellay J3.

Am J Hum Genet. 2015 Oct 6. pii: S0002-9297(15)00372-9. doi: 10.1016/j.ajhg.2015.09.008. [Epub ahead of print]

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