Genome-wide genetic investigation of serological measures of common infections

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 fa...

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Main Authors: Rubicz, R., Yolken, R., Drigalenko, E., Carless, M., Dyer, T., Kent, J., Curran, J., Johnson, M., Cole, S., Fowler, S., Arya, R., Puppala, S., Almasy, L., Moses, Eric, Kraig, E., Duggirala, R., Blangero, J., Leach, C., Göring, H.
Format: Journal Article
Published: 2015
Online Access:http://hdl.handle.net/20.500.11937/45651
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author Rubicz, R.
Yolken, R.
Drigalenko, E.
Carless, M.
Dyer, T.
Kent, J.
Curran, J.
Johnson, M.
Cole, S.
Fowler, S.
Arya, R.
Puppala, S.
Almasy, L.
Moses, Eric
Kraig, E.
Duggirala, R.
Blangero, J.
Leach, C.
Göring, H.
author_facet Rubicz, R.
Yolken, R.
Drigalenko, E.
Carless, M.
Dyer, T.
Kent, J.
Curran, J.
Johnson, M.
Cole, S.
Fowler, S.
Arya, R.
Puppala, S.
Almasy, L.
Moses, Eric
Kraig, E.
Duggirala, R.
Blangero, J.
Leach, C.
Göring, H.
author_sort Rubicz, R.
building Curtin Institutional Repository
collection Online Access
description 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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spelling curtin-20.500.11937-456512017-09-13T14:25:26Z Genome-wide genetic investigation of serological measures of common infections Rubicz, R. Yolken, R. Drigalenko, E. Carless, M. Dyer, T. Kent, J. Curran, J. Johnson, M. Cole, S. Fowler, S. Arya, R. Puppala, S. Almasy, L. Moses, Eric Kraig, E. Duggirala, R. Blangero, J. Leach, C. Göring, H. 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/45651 10.1038/ejhg.2015.24 unknown
spellingShingle Rubicz, R.
Yolken, R.
Drigalenko, E.
Carless, M.
Dyer, T.
Kent, J.
Curran, J.
Johnson, M.
Cole, S.
Fowler, S.
Arya, R.
Puppala, S.
Almasy, L.
Moses, Eric
Kraig, E.
Duggirala, R.
Blangero, J.
Leach, C.
Göring, H.
Genome-wide genetic investigation of serological measures of common infections
title Genome-wide genetic investigation of serological measures of common infections
title_full Genome-wide genetic investigation of serological measures of common infections
title_fullStr Genome-wide genetic investigation of serological measures of common infections
title_full_unstemmed Genome-wide genetic investigation of serological measures of common infections
title_short Genome-wide genetic investigation of serological measures of common infections
title_sort genome-wide genetic investigation of serological measures of common infections
url http://hdl.handle.net/20.500.11937/45651