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.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Rohina
authors.initials: R
authors.lastname: Rubicz
authors.affiliation: Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Drigalenko
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Kent
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Sharon P
authors.initials: SP
authors.lastname: Fowler
authors.affiliation: Division of Endocrinology and Diabetes, Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Rector
authors.initials: R
authors.lastname: Arya
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Sobha
authors.initials: S
authors.lastname: Puppala
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: Center for Genetic Epidemiology and Biostatistics, The University of Western Australia, Perth, WA, Australia.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kraig
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Ravindranath
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine/Children's Hospital of San Antonio, San Antonio, TX, USA.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Leach
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000235:genetics*; D000914:Antibodies, Viral / Q000097:blood / Q000235:genetics*; D001419:Bacteria / Q000145:classification / Q000276:immunology / Q000472:pathogenicity; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007239:Infections / Q000097:blood / Q000235:genetics* / Q000382:microbiology / Q000821:virology; D008126:Lod Score; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014780:Viruses / Q000145:classification / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D007074:Immunoglobulin G