Abstract
Populations and individuals differ in susceptibility to infections because of a number of factors, including host genetic variation. We previously demonstrated that differences in antibody titer, which reflect infection history, are significantly heritable. Here we attempt to identify the genetic factors influencing variation in these serological phenotypes. Blood samples from >1300 Mexican Americans were quantified for IgG antibody level against 12 common infections, selected on the basis of their reported role in cardiovascular disease risk: Chlamydia pneumoniae; Helicobacter pylori; Toxoplasma gondii; cytomegalovirus; herpes simplex I virus; herpes simplex II virus; human herpesvirus 6 (HHV6); human herpesvirus 8 (HHV8); varicella zoster virus; hepatitis A virus (HAV); influenza A virus; and influenza B virus. Pathogen-specific quantitative antibody levels were analyzed, as were three measures of pathogen burden. Genome-wide linkage and joint linkage and association analyses were performed using ~1 million SNPs. Significant linkage (lod scores >3.0) was obtained for HHV6 (on chromosome 7), HHV8 (on chromosome 6), and HAV (on chromosome 13). SNP rs4812712 on chromosome 20 was significantly associated with C. pneumoniae (P=5.3 × 10−8). However, no genome-wide significant loci were obtained for the other investigated antibodies. We conclude that it is possible to localize host genetic factors influencing some of these antibody traits, but that further larger-scale investigations will be required to elucidate the genetic mechanisms contributing to variation in antibody levels.
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Acknowledgements
We thank the participants of the San Antonio Family Heart Study and the San Antonio Family Diabetes/Gallbladder Study. We also thank Mr Barry Grubbs and Ms Bogdana Krivogorsky for their assistance in performing the antibody assays. This work is supported by grants from the US National Heart, Lung, and Blood Institute (HL045522 and HL080149) and the National Institute for Mental Health (MH078143, MH078111, and MH083824). Serological assays were supported in part by the Stanley Medical Research Institute. The statistical computer package SOLAR was supported by a grant from the US National Institute of Mental Health (MH059490). Analyses were conducted in facilities constructed with support from the National Center for Research Resources (RR017515) and a gift from the SBC Foundation. The National Institutes of Health LRP for health disparities research (L60 MD003255) provided additional support.
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Rubicz, R., Yolken, R., Drigalenko, E. et al. Genome-wide genetic investigation of serological measures of common infections. Eur J Hum Genet 23, 1544–1548 (2015). https://doi.org/10.1038/ejhg.2015.24
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DOI: https://doi.org/10.1038/ejhg.2015.24
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