Evidence for a Heritable Predisposition to Death Due to Influenza

Abstract

Animal model studies and human epidemiological studies have shown that some infectious diseases develop primarily in individuals with an inherited predisposition. A heritable contribution to the development of severe influenza virus infection (i.e., that which results in death) has not previously been hypothesized or tested. Evidence for a heritable contribution to death due to influenza was examined using a resource consisting of a genealogy of the Utah population linked to death certificates in Utah over a period of 100 years. The relative risks of death due to influenza were estimated for the relatives of 4,855 individuals who died of influenza. Both close and distant relatives of individuals who died of influenza were shown to have a significantly increased risk of dying of influenza, consistent with a combination of shared exposure and genetic effects. These data provide strong support for a heritable contribution to predisposition to death due to influenza.

Pandemic lessons from Iceland

“…The methods, and many of the results, were broadly similar to those of the Iceland investigation, but the conclusion appeared to be exactly the opposite-that there existed a heritable predisposition to death from influenza. Relatives of fatal influenza cases were at significantly (1) conclude that genetic susceptibility was not in fact the major driver of increased family risk, which was also the conclusion reached in a recent analysis of H5N1 clusters (8) and which appears broadly consistent with observations from Utah that showed the highest risk for spouses and elevated risks also for the siblings of spouses (9). Presumably, if genetics was a factor at all in Iceland, it was greatly outweighed by close contact between family or household members, whether related or not, who either provided care for the ill family member or were otherwise exposed.…”

Evidence for an Inherited Predisposition Contributing to the Risk for Rotator Cuff Disease

“…Methods for the analysis of the Utah Population Database genealogical and linked hospital data have been well reported and represent examination of a number of different phenotypes [7][8][9] . Analysis of the familial clustering includes comparing the average relatedness between all pairs of patients and the expected average relatedness with use of the Genealogical Index of Familiality.…”

“…The University of Utah Health Sciences Center data warehouse, representing patient information from University of Utah Hospital and Clinics since 1994, has been linked to the Utah Population Database genealogical data. This combined database is a unique and invaluable resource for evaluating familial clustering for a variety of disease processes [7][8][9] .…”

Creation of a national resource with linked genealogy and phenotypic data: the Veterans Genealogy Project

“…These two resources have proven extremely valuable in understanding the genetic contribution to complex phenotypes [2][3][4][5][6][7][8][9][10] and in predisposition gene identification. [11][12][13][14][15] The Veterans Genealogy Project reported here proposes extension of this general concept by creation of a genealogy/biomedical resource for the United States and its immigrant founders.…”