Common genetic variation influencing human white matter microstructure

Bingxin Zhao; Tengfei Li; Yue Yang; Xifeng Wang; Tianyou Luo; Yue Shan; Ziliang Zhu; Di Xiong; Mads E Hauberg; Jaroslav Bendl; John F Fullard; Panagiotis Roussos; Yun Li; Jason L Stein; Hongtu Zhu

doi:10.1126/science.abf3736

Common genetic variation influencing human white matter microstructure

Science. 2021 Jun 18;372(6548):eabf3736. doi: 10.1126/science.abf3736.

Authors

Bingxin Zhao^#¹, Tengfei Li^#^{2

3}, Yue Yang⁴, Xifeng Wang⁴, Tianyou Luo⁴, Yue Shan⁴, Ziliang Zhu⁴, Di Xiong⁴, Mads E Hauberg^{5

6

7

8}, Jaroslav Bendl^{5

9

6}, John F Fullard^{5

9

6}, Panagiotis Roussos^{5

9

6

10}, Yun Li^{4

11

12}, Jason L Stein^{11

13}, Hongtu Zhu^{14

4}

Affiliations

¹ Department of Statistics, Purdue University, West Lafayette, IN 47907, USA.
² Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Biomedical Research Imaging Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁶ Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁷ iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 8210 Aarhus, Denmark.
⁸ Centre for Integrative Sequencing (iSEQ), Aarhus University, 8000 Aarhus, Denmark.
⁹ Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁰ Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY 10468, USA.
¹¹ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹² Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹³ UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁴ Biomedical Research Imaging Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. htzhu@email.unc.edu.

^# Contributed equally.

Abstract

Brain regions communicate with each other through tracts of myelinated axons, commonly referred to as white matter. We identified common genetic variants influencing white matter microstructure using diffusion magnetic resonance imaging of 43,802 individuals. Genome-wide association analysis identified 109 associated loci, 30 of which were detected by tract-specific functional principal components analysis. A number of loci colocalized with brain diseases, such as glioma and stroke. Genetic correlations were observed between white matter microstructure and 57 complex traits and diseases. Common variants associated with white matter microstructure altered the function of regulatory elements in glial cells, particularly oligodendrocytes. This large-scale tract-specific study advances the understanding of the genetic architecture of white matter and its genetic links to a wide spectrum of clinical outcomes.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Brain / anatomy & histology
Brain / physiology
Brain Diseases / genetics
Cognition
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
Female
Genetic Variation*
Genome, Human
Genome-Wide Association Study
Heart Disease Risk Factors
Humans
Male
Mental Disorders / genetics
Multifactorial Inheritance
Neural Pathways
Neuroglia / physiology
Neurons / physiology
Principal Component Analysis
Quantitative Trait Loci
Risk Factors
White Matter / diagnostic imaging
White Matter / physiology*
White Matter / ultrastructure*

Abstract

Publication types

MeSH terms

Grants and funding