Genetic Factors Influence Serological Measures of Common Infections

Abstract

Background/Aims: Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods: IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and -2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results: Serological phenotypes were significantly heritable for most pathogens (h² = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c² = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions: Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance.

Genome-wide genetic investigation of serological measures of common infections

“…Our contention that seronegative individuals do provide host genetic information is supported by our previous demonstration that these antibody level traits are substantially heritable when one includes seronegative individuals in the analysis, with the smallest heritability estimate obtained for the sexually transmitted HSV-2 (in which case seronegative individuals may well have not been exposed at all and thus would not provide any information on host genetics). 6 It should be noted that antibody level does not necessarily correlate with Bold = genome-wide significant at P ≤ 1.3 × 10 − 7 ; significance threshold was estimated on the basis of our sample of Mexican-American participants. The threshold for suggestive evidence for association used here is P ≤ 1.3 × 10 -6 .…”

“…The seroprevalence rates for these pathogens ranged from 10% for T. gondii to 92% for VZV (Table 1), and are described in greater detail in the study by Rubicz et al 18 Heritability estimates were significant for all pathogens, ranging from 0.08 for HSV-2 to 0.37 for HHV-8 ( Table 1 and Rubicz et al). 6 Three measures of pathogen burden (ie, the number of seropositive reactions to the investigated pathogens) were generated -namely, for all herpes viruses, all viruses, and all pathogens. These three burden traits were also significantly heritable, with heritability estimates between 0.16 and 0.24.…”

“…[3][4][5] We previously demonstrated that differences in antibody titer, which reflect infection history, are significantly heritable for a number of common infectious pathogens. 6 Here we attempt to localize the genetic factors influencing serological phenotypes of these pathogens using genome-wide statistical gene-mapping approaches. We had selected 12 pathogens for examination because of reports linking them to risk for cardiovascular disease.…”

Validation of diagnostic tests and epidemiology of Helicobacter pylori infection in Bangladesh

“…Campylobacter etc. in endemic area also influence the antibody based diagnostic tests [41]. The performance of ELISA is also directly related with the antibody concentration.…”

The role of cytokines and inflammatory markers in depression in adolescents

“…With regard to antibody levels, the low heritability estimates measured were in contrast to the observations of another study. Specifically, heritabilities for CMV and HHV-6 antibody levels were observed to be 0.39 and 0.28 respectively, with small common environmental contributions to the variance of levels of these particular antibodies (289).…”