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Evidence for a Heritable Predisposition to Fatal Influenza

By Luciana Borio, M.D., December 19, 2007

A recent study by Albright and colleagues1 from the University of Utah School of Medicine supports the hypothesis that there exists an inherited predisposition to developing and dying from severe influenza. There are other infections for which genetic predisposition has been shown to play a role in disease severity,2 but this is the first study that looked at such predisposition with influenza. Demonstrating a heritable contribution to death due to influenza is particularly challenging since familial clusters of disease might also be caused by shared exposure to the same virulent virus.

Using the Utah Population Data Base (UPDB), a genealogical resource that includes data for the original Utah pioneers and their descendants, the researchers examined death certificates in Utah over a period of 100 years. In order to estimate the relative risk of death from influenza for the relatives of 4,855 individuals who died of influenza between 1904 and 2004, the researchers compared the observed rate of influenza deaths among relatives with the expected rate of influenza deaths in the population. Results are summarized in the table below.

Table: Relative risk (RR) of death due to influenza among the relatives and spouses of individuals dying of influenza

All first-degree1.54

The elevated RRs observed in spouses most likely results from shared exposure. The authors explain that “increased RRs for first-degree relatives cannot distinguish between the results of shared genetics or shared effects of environment and/or exposure, because first-degree relatives have these types of effects in common. Significantly elevated RRs in more distant relatives, however, provide strong support for a heritable contribution. Distant relatives share more genes but fewer effects of exposure and/or environment with each other than with individuals in the general population.” To further distinguish between a heritable predisposition and the effects of a common environment, the researchers compared the RRs for relatives of individuals dying of influenza with the RRs for relatives of spouses of individuals dying of influenza. They found that the estimated RRs for relatives of individuals dying of influenza were higher than the RRs for the relatives of their spouses, providing additional support to their hypothesis.

Influenza is a spectrum disease of variable morbidity that causes asymptomatic infection or symptoms that range from mild to severe disease and death. Although seasonal influenza affects 10% to 25% of the global population every year, only a fraction dies from it. Understanding the host factors that account for greater susceptibility to severe infection and death is important in the development of sound policies for protecting the greatest number of people and lessening the impact of epidemics and pandemics. Up to now, only age and comorbid conditions were considered host risk factors for serious influenza infection. Much more research is needed to elucidate the exact host genetic factors that play a role in influenza severity.


  1. Albright FS, Orlando P, and Pavia AT, et al. Evidence for a heritable predisposition to death due to influenza. J Infect Dis 2008:197.
    . Accessed December 18, 2007.

  2. See for instance: Sancho-Shimizu V, Zhang SY, Abel L, et al. Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans.  Curr Opin Allergy Clin Immunol 2007;7:495-505.
    . Accessed December 18, 2007.

Additional Reading: Samira M and Palese. Editorial and Commentary: Human Genes and Influenza. J Infect Dis 2008:197. Accessed December 18, 2007.