---
_id: '8133'
abstract:
- lang: eng
  text: The molecular factors which control circulating levels of inflammatory proteins
    are not well understood. Furthermore, association studies between molecular probes
    and human traits are often performed by linear model-based methods which may fail
    to account for complex structure and interrelationships within molecular datasets.In
    this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS)
    on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy
    older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel).
    We employ a Bayesian framework (BayesR+) which can account for issues pertaining
    to data structure and unknown confounding variables (with sensitivity analyses
    using ordinary least squares- (OLS) and mixed model-based approaches). We identified
    13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and
    Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG
    each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged
    genetic variants accounted for up to 45% of variance in protein levels (for MCP2,
    36% of variance alone attributable to 1 polymorphism). Methylation data accounted
    for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation
    in protein levels (for VEGFA) was explained using genetic and epigenetic data
    combined. We demonstrated putative causal relationships between CD6 and IL18R1
    with inflammatory bowel disease and between IL12B and Crohn’s disease. Our data
    may aid understanding of the molecular regulation of the circulating inflammatory
    proteome as well as causal relationships between inflammatory mediators and disease.
article_number: '60'
article_processing_charge: No
article_type: original
author:
- first_name: Robert F.
  full_name: Hillary, Robert F.
  last_name: Hillary
- first_name: Daniel
  full_name: Trejo-Banos, Daniel
  last_name: Trejo-Banos
- first_name: Athanasios
  full_name: Kousathanas, Athanasios
  last_name: Kousathanas
- first_name: Daniel L.
  full_name: Mccartney, Daniel L.
  last_name: Mccartney
- first_name: Sarah E.
  full_name: Harris, Sarah E.
  last_name: Harris
- first_name: Anna J.
  full_name: Stevenson, Anna J.
  last_name: Stevenson
- first_name: Marion
  full_name: Patxot, Marion
  last_name: Patxot
- first_name: Sven Erik
  full_name: Ojavee, Sven Erik
  last_name: Ojavee
- first_name: Qian
  full_name: Zhang, Qian
  last_name: Zhang
- first_name: David C.
  full_name: Liewald, David C.
  last_name: Liewald
- first_name: Craig W.
  full_name: Ritchie, Craig W.
  last_name: Ritchie
- first_name: Kathryn L.
  full_name: Evans, Kathryn L.
  last_name: Evans
- first_name: Elliot M.
  full_name: Tucker-Drob, Elliot M.
  last_name: Tucker-Drob
- first_name: Naomi R.
  full_name: Wray, Naomi R.
  last_name: Wray
- first_name: Allan F.
  full_name: Mcrae, Allan F.
  last_name: Mcrae
- first_name: Peter M.
  full_name: Visscher, Peter M.
  last_name: Visscher
- first_name: Ian J.
  full_name: Deary, Ian J.
  last_name: Deary
- first_name: Matthew Richard
  full_name: Robinson, Matthew Richard
  id: E5D42276-F5DA-11E9-8E24-6303E6697425
  last_name: Robinson
  orcid: 0000-0001-8982-8813
- first_name: Riccardo E.
  full_name: Marioni, Riccardo E.
  last_name: Marioni
citation:
  ama: Hillary RF, Trejo-Banos D, Kousathanas A, et al. Multi-method genome- and epigenome-wide
    studies of inflammatory protein levels in healthy older adults. <i>Genome Medicine</i>.
    2020;12(1). doi:<a href="https://doi.org/10.1186/s13073-020-00754-1">10.1186/s13073-020-00754-1</a>
  apa: Hillary, R. F., Trejo-Banos, D., Kousathanas, A., Mccartney, D. L., Harris,
    S. E., Stevenson, A. J., … Marioni, R. E. (2020). Multi-method genome- and epigenome-wide
    studies of inflammatory protein levels in healthy older adults. <i>Genome Medicine</i>.
    Springer Nature. <a href="https://doi.org/10.1186/s13073-020-00754-1">https://doi.org/10.1186/s13073-020-00754-1</a>
  chicago: Hillary, Robert F., Daniel Trejo-Banos, Athanasios Kousathanas, Daniel
    L. Mccartney, Sarah E. Harris, Anna J. Stevenson, Marion Patxot, et al. “Multi-Method
    Genome- and Epigenome-Wide Studies of Inflammatory Protein Levels in Healthy Older
    Adults.” <i>Genome Medicine</i>. Springer Nature, 2020. <a href="https://doi.org/10.1186/s13073-020-00754-1">https://doi.org/10.1186/s13073-020-00754-1</a>.
  ieee: R. F. Hillary <i>et al.</i>, “Multi-method genome- and epigenome-wide studies
    of inflammatory protein levels in healthy older adults,” <i>Genome Medicine</i>,
    vol. 12, no. 1. Springer Nature, 2020.
  ista: Hillary RF, Trejo-Banos D, Kousathanas A, Mccartney DL, Harris SE, Stevenson
    AJ, Patxot M, Ojavee SE, Zhang Q, Liewald DC, Ritchie CW, Evans KL, Tucker-Drob
    EM, Wray NR, Mcrae AF, Visscher PM, Deary IJ, Robinson MR, Marioni RE. 2020. Multi-method
    genome- and epigenome-wide studies of inflammatory protein levels in healthy older
    adults. Genome Medicine. 12(1), 60.
  mla: Hillary, Robert F., et al. “Multi-Method Genome- and Epigenome-Wide Studies
    of Inflammatory Protein Levels in Healthy Older Adults.” <i>Genome Medicine</i>,
    vol. 12, no. 1, 60, Springer Nature, 2020, doi:<a href="https://doi.org/10.1186/s13073-020-00754-1">10.1186/s13073-020-00754-1</a>.
  short: R.F. Hillary, D. Trejo-Banos, A. Kousathanas, D.L. Mccartney, S.E. Harris,
    A.J. Stevenson, M. Patxot, S.E. Ojavee, Q. Zhang, D.C. Liewald, C.W. Ritchie,
    K.L. Evans, E.M. Tucker-Drob, N.R. Wray, A.F. Mcrae, P.M. Visscher, I.J. Deary,
    M.R. Robinson, R.E. Marioni, Genome Medicine 12 (2020).
date_created: 2020-07-19T22:00:58Z
date_published: 2020-07-08T00:00:00Z
date_updated: 2023-08-22T07:55:37Z
day: '08'
ddc:
- '570'
department:
- _id: MaRo
doi: 10.1186/s13073-020-00754-1
external_id:
  isi:
  - '000551778400001'
  pmid:
  - '32641083'
file:
- access_level: open_access
  content_type: application/pdf
  creator: dernst
  date_created: 2020-07-22T06:27:38Z
  date_updated: 2020-07-22T06:27:38Z
  file_id: '8145'
  file_name: 2020_GenomeMedicine_Hillary.pdf
  file_size: 1136983
  relation: main_file
  success: 1
file_date_updated: 2020-07-22T06:27:38Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: Genome Medicine
publication_identifier:
  eissn:
  - 1756994X
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '9706'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Multi-method genome- and epigenome-wide studies of inflammatory protein levels
  in healthy older adults
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2020'
...