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Hum Brain Mapp. 2019 Oct 1;40(14):4180-4191. doi: 10.1002/hbm.24694. Epub 2019 Jun 11.

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

Author information

1
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
2
Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
3
Department of Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas of the Rio Grande Valley, Brownsville, Texas.
4
Research Imaging Institute, University of Texas Health San Antonio, San Antonio, Texas.
5
Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
6
Department of Cognitive Neuroscience, Radboudumc, Nijmegen, the Netherlands.
7
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
8
Department of Psychiatry, University of Texas Health San Antonio, San Antonio, Texas.
9
Department of Genetics, Perelman School of Medicine and the Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
10
Olin Neuropsychiatry Research Center, Institute of Living, Hartford, Connecticut.

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.

KEYWORDS:

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

PMID:
31187567
PMCID:
PMC6707845
[Available on 2020-10-01]
DOI:
10.1002/hbm.24694

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