Whole blood gene expression and white matter Hyperintensities

Honghuang Lin; Claudia Satizabal; Zhijun Xie; Qiong Yang; Tianxiao Huan; Roby Joehanes; Chengping Wen; Peter J Munson; Alexa Beiser; Daniel Levy; Sudha Seshadri

doi:10.1186/s13024-017-0209-5

Whole blood gene expression and white matter Hyperintensities

Mol Neurodegener. 2017 Sep 18;12(1):67. doi: 10.1186/s13024-017-0209-5.

Authors

Honghuang Lin^{1

2}, Claudia Satizabal^{3

4}, Zhijun Xie⁵, Qiong Yang⁶, Tianxiao Huan^{3

7}, Roby Joehanes^{8

9}, Chengping Wen⁵, Peter J Munson⁸, Alexa Beiser^{3

4

6}, Daniel Levy^{3

7}, Sudha Seshadri^{10

11}

Affiliations

¹ National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA. [email protected].
² Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, B-616, Boston, MA, 02118, USA. [email protected].
³ National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.
⁴ Department of Neurology, Boston University School of Medicine, 72 East Concord Street, B-602, Boston, MA, 02118, USA.
⁵ College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
⁶ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁷ Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
⁸ Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institute of Health, Bethesda, MD, USA.
⁹ Hebrew Senior Life, 1200 Centre Street Room #609, Boston, MA, 02131, USA.
¹⁰ National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA. [email protected].
¹¹ Department of Neurology, Boston University School of Medicine, 72 East Concord Street, B-602, Boston, MA, 02118, USA. [email protected].

Abstract

Background: White matter hyperintensities (WMH) are an important biomarker of cumulative vascular brain injury and have been associated with cognitive decline and an increased risk of dementia, stroke, depression, and gait impairments. The pathogenesis of white matter lesions however, remains uncertain. The characterization of gene expression profiles associated with WMH might help uncover molecular mechanisms underlying WMH.

Methods: We performed a transcriptome-wide association study of gene expression profiles with WMH in 3248 participants from the Framingham Heart Study using the Affymetrix Human Exon 1.0 ST Array.

Results: We identified 13 genes that were significantly associated with WMH (FDR < 0.05) after adjusting for age, sex and blood cell components. Many of these genes are involved in inflammation-related pathways.

Conclusion: Thirteen genes were significantly associated with WMH. Our study confirms the hypothesis that inflammation might be an important factor contributing to white matter lesions. Future work is needed to explore if these gene products might serve as potential therapeutic targets.

Keywords: Epidemiology; Gene expression; White matter hyperintensities.

MeSH terms

Adult
Aged
Brain / pathology*
Female
Humans
Male
Middle Aged
Prospective Studies
Transcriptome*
White Matter / pathology*

Abstract

MeSH terms

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