Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens

Rohina Rubicz, Robert Yolken, Armin Alaedini, Eugene Drigalenko, Jac C. Charlesworth, Melanie A. Carless, Emily G. Severance, Bogdana Krivogorsky, Thomas D. Dyer, Jack W. Kent, Joanne E. Curran, Matthew P. Johnson, Shelley A. Cole, Laura Almasy, Eric K. Moses, John Blangero, Harald H H Göring

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Increased immunoglobulin G (IgG) response to dietary antigens can be associated with gastrointestinal dysfunction and autoimmunity. The underlying processes contributing to these adverse reactions remain largely unknown, and it is likely that genetic factors play a role. Here, we estimate heritability and attempt to localize genetic factors influencing IgG antibody levels against food-derived antigens using an integrative genomics approach. IgG antibody levels were determined by ELISA in >1,300 Mexican Americans for the following food antigens: wheat gliadin; bovine casein; and two forms of bovine serum albumin (BSA-a and BSA-b). Pedigree-based variance components methods were used to estimate additive genetic heritability (h2), perform genome-wide association analyses, and identify transcriptional signatures (based on 19,858 transcripts from peripheral blood lymphocytes). Heritability estimates were significant for all traits (0.15-0.53), and shared environment (based on shared residency among study participants) was significant for casein (0.09) and BSA-a (0.33). Genome-wide significant evidence of association was obtained only for antibody to gliadin (P = 8.57 × 10-8), mapping to the human leukocyte antigen II region, with HLA-DRA and BTNL2 as the best candidate genes. Lack of association of known celiac disease risk alleles HLA-DQ2.5 and -DQ8 with antigliadin antibodies in the studied population suggests a separate genetic etiology. Significant transcriptional signatures were found for all IgG levels except BSA-b. These results demonstrate that individual genetic differences contribute to food antigen antibody measures in this population. Further investigations may elucidate the underlying immunological processes involved.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalGenetic Epidemiology
Volume38
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Antibody Formation
Genome
Antigens
Immunoglobulin G
Antibodies
Gliadin
Caseins
Food
HLA-DR alpha-Chains
Genome-Wide Association Study
Celiac Disease
Pedigree
Internship and Residency
HLA Antigens
Bovine Serum Albumin
Genomics
Autoimmunity
Individuality
Population
Triticum

Keywords

  • Association
  • Gliadin
  • IgG antibody
  • Integrative genomics
  • Pedigree study
  • Transcriptional profiling

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Rubicz, R., Yolken, R., Alaedini, A., Drigalenko, E., Charlesworth, J. C., Carless, M. A., ... Göring, H. H. H. (2014). Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens. Genetic Epidemiology, 38(5), 439-446. https://doi.org/10.1002/gepi.21817

Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens. / Rubicz, Rohina; Yolken, Robert; Alaedini, Armin; Drigalenko, Eugene; Charlesworth, Jac C.; Carless, Melanie A.; Severance, Emily G.; Krivogorsky, Bogdana; Dyer, Thomas D.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Cole, Shelley A.; Almasy, Laura; Moses, Eric K.; Blangero, John; Göring, Harald H H.

In: Genetic Epidemiology, Vol. 38, No. 5, 2014, p. 439-446.

Research output: Contribution to journalArticle

Rubicz, R, Yolken, R, Alaedini, A, Drigalenko, E, Charlesworth, JC, Carless, MA, Severance, EG, Krivogorsky, B, Dyer, TD, Kent, JW, Curran, JE, Johnson, MP, Cole, SA, Almasy, L, Moses, EK, Blangero, J & Göring, HHH 2014, 'Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens', Genetic Epidemiology, vol. 38, no. 5, pp. 439-446. https://doi.org/10.1002/gepi.21817
Rubicz, Rohina ; Yolken, Robert ; Alaedini, Armin ; Drigalenko, Eugene ; Charlesworth, Jac C. ; Carless, Melanie A. ; Severance, Emily G. ; Krivogorsky, Bogdana ; Dyer, Thomas D. ; Kent, Jack W. ; Curran, Joanne E. ; Johnson, Matthew P. ; Cole, Shelley A. ; Almasy, Laura ; Moses, Eric K. ; Blangero, John ; Göring, Harald H H. / Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens. In: Genetic Epidemiology. 2014 ; Vol. 38, No. 5. pp. 439-446.
@article{0eaae8c69a4648a0b616fedafbea040a,
title = "Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens",
abstract = "Increased immunoglobulin G (IgG) response to dietary antigens can be associated with gastrointestinal dysfunction and autoimmunity. The underlying processes contributing to these adverse reactions remain largely unknown, and it is likely that genetic factors play a role. Here, we estimate heritability and attempt to localize genetic factors influencing IgG antibody levels against food-derived antigens using an integrative genomics approach. IgG antibody levels were determined by ELISA in >1,300 Mexican Americans for the following food antigens: wheat gliadin; bovine casein; and two forms of bovine serum albumin (BSA-a and BSA-b). Pedigree-based variance components methods were used to estimate additive genetic heritability (h2), perform genome-wide association analyses, and identify transcriptional signatures (based on 19,858 transcripts from peripheral blood lymphocytes). Heritability estimates were significant for all traits (0.15-0.53), and shared environment (based on shared residency among study participants) was significant for casein (0.09) and BSA-a (0.33). Genome-wide significant evidence of association was obtained only for antibody to gliadin (P = 8.57 × 10-8), mapping to the human leukocyte antigen II region, with HLA-DRA and BTNL2 as the best candidate genes. Lack of association of known celiac disease risk alleles HLA-DQ2.5 and -DQ8 with antigliadin antibodies in the studied population suggests a separate genetic etiology. Significant transcriptional signatures were found for all IgG levels except BSA-b. These results demonstrate that individual genetic differences contribute to food antigen antibody measures in this population. Further investigations may elucidate the underlying immunological processes involved.",
keywords = "Association, Gliadin, IgG antibody, Integrative genomics, Pedigree study, Transcriptional profiling",
author = "Rohina Rubicz and Robert Yolken and Armin Alaedini and Eugene Drigalenko and Charlesworth, {Jac C.} and Carless, {Melanie A.} and Severance, {Emily G.} and Bogdana Krivogorsky and Dyer, {Thomas D.} and Kent, {Jack W.} and Curran, {Joanne E.} and Johnson, {Matthew P.} and Cole, {Shelley A.} and Laura Almasy and Moses, {Eric K.} and John Blangero and G{\"o}ring, {Harald H H}",
year = "2014",
doi = "10.1002/gepi.21817",
language = "English (US)",
volume = "38",
pages = "439--446",
journal = "Genetic Epidemiology",
issn = "0741-0395",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens

AU - Rubicz, Rohina

AU - Yolken, Robert

AU - Alaedini, Armin

AU - Drigalenko, Eugene

AU - Charlesworth, Jac C.

AU - Carless, Melanie A.

AU - Severance, Emily G.

AU - Krivogorsky, Bogdana

AU - Dyer, Thomas D.

AU - Kent, Jack W.

AU - Curran, Joanne E.

AU - Johnson, Matthew P.

AU - Cole, Shelley A.

AU - Almasy, Laura

AU - Moses, Eric K.

AU - Blangero, John

AU - Göring, Harald H H

PY - 2014

Y1 - 2014

N2 - Increased immunoglobulin G (IgG) response to dietary antigens can be associated with gastrointestinal dysfunction and autoimmunity. The underlying processes contributing to these adverse reactions remain largely unknown, and it is likely that genetic factors play a role. Here, we estimate heritability and attempt to localize genetic factors influencing IgG antibody levels against food-derived antigens using an integrative genomics approach. IgG antibody levels were determined by ELISA in >1,300 Mexican Americans for the following food antigens: wheat gliadin; bovine casein; and two forms of bovine serum albumin (BSA-a and BSA-b). Pedigree-based variance components methods were used to estimate additive genetic heritability (h2), perform genome-wide association analyses, and identify transcriptional signatures (based on 19,858 transcripts from peripheral blood lymphocytes). Heritability estimates were significant for all traits (0.15-0.53), and shared environment (based on shared residency among study participants) was significant for casein (0.09) and BSA-a (0.33). Genome-wide significant evidence of association was obtained only for antibody to gliadin (P = 8.57 × 10-8), mapping to the human leukocyte antigen II region, with HLA-DRA and BTNL2 as the best candidate genes. Lack of association of known celiac disease risk alleles HLA-DQ2.5 and -DQ8 with antigliadin antibodies in the studied population suggests a separate genetic etiology. Significant transcriptional signatures were found for all IgG levels except BSA-b. These results demonstrate that individual genetic differences contribute to food antigen antibody measures in this population. Further investigations may elucidate the underlying immunological processes involved.

AB - Increased immunoglobulin G (IgG) response to dietary antigens can be associated with gastrointestinal dysfunction and autoimmunity. The underlying processes contributing to these adverse reactions remain largely unknown, and it is likely that genetic factors play a role. Here, we estimate heritability and attempt to localize genetic factors influencing IgG antibody levels against food-derived antigens using an integrative genomics approach. IgG antibody levels were determined by ELISA in >1,300 Mexican Americans for the following food antigens: wheat gliadin; bovine casein; and two forms of bovine serum albumin (BSA-a and BSA-b). Pedigree-based variance components methods were used to estimate additive genetic heritability (h2), perform genome-wide association analyses, and identify transcriptional signatures (based on 19,858 transcripts from peripheral blood lymphocytes). Heritability estimates were significant for all traits (0.15-0.53), and shared environment (based on shared residency among study participants) was significant for casein (0.09) and BSA-a (0.33). Genome-wide significant evidence of association was obtained only for antibody to gliadin (P = 8.57 × 10-8), mapping to the human leukocyte antigen II region, with HLA-DRA and BTNL2 as the best candidate genes. Lack of association of known celiac disease risk alleles HLA-DQ2.5 and -DQ8 with antigliadin antibodies in the studied population suggests a separate genetic etiology. Significant transcriptional signatures were found for all IgG levels except BSA-b. These results demonstrate that individual genetic differences contribute to food antigen antibody measures in this population. Further investigations may elucidate the underlying immunological processes involved.

KW - Association

KW - Gliadin

KW - IgG antibody

KW - Integrative genomics

KW - Pedigree study

KW - Transcriptional profiling

UR - http://www.scopus.com/inward/record.url?scp=84902995993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902995993&partnerID=8YFLogxK

U2 - 10.1002/gepi.21817

DO - 10.1002/gepi.21817

M3 - Article

VL - 38

SP - 439

EP - 446

JO - Genetic Epidemiology

JF - Genetic Epidemiology

SN - 0741-0395

IS - 5

ER -