title: Heritability of vaccine-induced measles neutralizing antibody titers.
abstract: Understanding how genetics influences inter-individual variation of antibody titers in response to measles vaccination is vital to understanding possible sources of vaccine failure as well as improved vaccine development. Although it is recognized that both the human leukocyte antigen (HLA) genes and the immunoglobulin allotype genes play significant roles in immune response, there is significant variation in antibody titers that is not explained by these genes. To obtain a more complete estimate of the role of the entire genome, we used a large panel of single nucleotide polymorphisms to estimate the heritability of antibody response to measles vaccine. Based on 935 subjects with European ancestry, we estimated the heritability to be 49% (standard error 0.17). We also estimated the heritability attributable to each chromosome, and found a large range in chromosome-specific heritabilities. Notably, chromosome 1 had the largest estimate (28%), while chromosome 6, which harbors HLA, had an estimated heritability of 13%. Compared with a prior study of twins in the same community, which resulted in a heritability estimate of 88.5%, our study suggests there are either many rare genetic variants, or many common genetic variants of small effect sizes that contribute to variations of antibody titers in response to measles vaccine.
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Beth R
authors.initials: BR
authors.lastname: Larrabee
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: poland.gregory@mayo.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics*; D008297:Male; D008457:Measles / Q000276:immunology* / Q000517:prevention & control*; D008458:Measles Vaccine / Q000008:administration & dosage / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D008458:Measles Vaccine
keywords: Adult; Cellular; Genetic variation; Genome-wide association study; Heritability; Humoral; Immunity; Measles; Measles vaccine; Polymorphism; Single nucleotide