Genome-wide genetic investigation of serological measures of common infections

Rohina Rubicz; Robert Yolken; Eugene Drigalenko; Melanie A. Carless; Thomas D. Dyer; Jack Kent; Joanne E. Curran; Matthew P. Johnson; Shelley A. Cole; Sharon P. Fowler; Rector Arya; Sobha Puppala; Laura Almasy; Eric K. Moses; Ellen Kraig; Ravindranath Duggirala; John Blangero; Charles T. Leach; Harald H.H. Göring

doi:10.1038/ejhg.2015.24

Genome-wide genetic investigation of serological measures of common infections

Rohina Rubicz, Robert Yolken, Eugene Drigalenko, Melanie A. Carless, Thomas D. Dyer, Jack Kent, Joanne E. Curran, Matthew P. Johnson, Shelley A. Cole, Sharon P. Fowler, Rector Arya, Sobha Puppala, Laura Almasy, Eric K. Moses, Ellen Kraig, Ravindranath Duggirala, John Blangero, Charles T. Leach, Harald H.H. Göring

School of Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1544-1548
Number of pages	5
Journal	European Journal of Human Genetics
Volume	23
Issue number	11
DOIs	https://doi.org/10.1038/ejhg.2015.24
State	Published - Oct 1 2015

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1038/ejhg.2015.24

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Rubicz, R., Yolken, R., Drigalenko, E., Carless, M. A., Dyer, T. D., Kent, J., Curran, J. E., Johnson, M. P., Cole, S. A., Fowler, S. P., Arya, R., Puppala, S., Almasy, L., Moses, E. K., Kraig, E., Duggirala, R., Blangero, J., Leach, C. T., & Göring, H. H. H. (2015). Genome-wide genetic investigation of serological measures of common infections. European Journal of Human Genetics, 23(11), 1544-1548. https://doi.org/10.1038/ejhg.2015.24

Rubicz, R, Yolken, R, Drigalenko, E, Carless, MA, Dyer, TD, Kent, J, Curran, JE, Johnson, MP, Cole, SA, Fowler, SP, Arya, R, Puppala, S, Almasy, L, Moses, EK, Kraig, E, Duggirala, R, Blangero, J, Leach, CT & Göring, HHH 2015, 'Genome-wide genetic investigation of serological measures of common infections', European Journal of Human Genetics, vol. 23, no. 11, pp. 1544-1548. https://doi.org/10.1038/ejhg.2015.24

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title = "Genome-wide genetic investigation of serological measures of common infections",

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.",

author = "Rohina Rubicz and Robert Yolken and Eugene Drigalenko and Carless, {Melanie A.} and Dyer, {Thomas D.} and Jack Kent and Curran, {Joanne E.} and Johnson, {Matthew P.} and Cole, {Shelley A.} and Fowler, {Sharon P.} and Rector Arya and Sobha Puppala and Laura Almasy and Moses, {Eric K.} and Ellen Kraig and Ravindranath Duggirala and John Blangero and Leach, {Charles T.} and G{\"o}ring, {Harald H.H.}",

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year = "2015",

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doi = "10.1038/ejhg.2015.24",

language = "English (US)",

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AU - Rubicz, Rohina

AU - Yolken, Robert

AU - Drigalenko, Eugene

AU - Carless, Melanie A.

AU - Dyer, Thomas D.

AU - Kent, Jack

AU - Curran, Joanne E.

AU - Johnson, Matthew P.

AU - Cole, Shelley A.

AU - Fowler, Sharon P.

AU - Arya, Rector

AU - Puppala, Sobha

AU - Almasy, Laura

AU - Moses, Eric K.

AU - Kraig, Ellen

AU - Duggirala, Ravindranath

AU - Blangero, John

AU - Leach, Charles T.

AU - Göring, Harald H.H.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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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JF - European Journal of Human Genetics

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ER -

Genome-wide genetic investigation of serological measures of common infections

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