Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

Amanda L. Rodrigue, Emma E.M. Knowles, Josephine Mollon, Samuel R. Mathias, Marinka M.G. Koenis, Juan M. Peralta, Ana C. Leandro, Peter T. Fox, Emma Sprooten, Peter Kochunov, Rene L. Olvera, Ravindranath Duggirala, Laura A Almasy, Joanne E Curran, John C Blangero, David C. Glahn

Research output: Contribution to journalArticlepeer-review

Abstract

White matter microstructure is affected by immune system activity via the actions of circulating pro-inflammatory cytokines. Although white matter microstructure and inflammatory measures are significantly heritable, it is unclear if overlapping genetic factors influence these traits in humans. We conducted genetic correlation analyses of these traits using randomly ascertained extended pedigrees from the Genetics of Brain Structure and Function Study (N = 1862, 59% females, ages 18–97 years; 42 ± 15.7). White matter microstructure was assessed using fractional anisotropy (FA) calculated from diffusion tensor imaging (DTI). Circulating levels (pg/mL) of pro-inflammatory cytokines (IL-6, IL-8, and TNFα) phenotypically associated with white matter microstructure were quantified from blood serum. All traits were significantly heritable (h2 ranging from 0.41 to 0.66 for DTI measures and from 0.18 to 0.30 for inflammatory markers). Phenotypically, higher levels of circulating inflammatory markers were associated with lower FA values across the brain (r = −.03 to r = −.17). There were significant negative genetic correlations between most DTI measures and IL-8 and TNFα, although effects for TNFα were no longer significant when covarying for body mass index. Genetic correlations between DTI measures and IL-6 were not significant. Understanding the genetic correlation between specific inflammatory markers and DTI measures may help researchers focus questions related to inflammatory processes and brain structure.

Original languageEnglish (US)
Pages (from-to)4180-4191
Number of pages12
JournalHuman Brain Mapping
Volume40
Issue number14
DOIs
StatePublished - Jan 1 2019

Keywords

  • diffusion tensor imaging
  • genetic correlation
  • interleukin-6
  • interleukin-8
  • tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Evidence for genetic correlation between human cerebral white matter microstructure and inflammation'. Together they form a unique fingerprint.

Cite this