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Cited by 52Genetic Associations and EpidemiologyCerebrospinal fluid and hydrocephalusCerebrovascular and genetic disorders

Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

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Vojinovic, Dina, Adams, Hieab H., Jian, Xueqiu, Yang, Qiong, Smith, Albert Vernon, Bis, Joshua C., Teumer, Alexander, Scholz, Markus +83 more·2018·Nature Communications
DOI 10.1038/s41467-018-06234-wPMC PMC6158214
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Abstract

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = −0.59, p-value = 3.14 × 10−6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.

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  • The C16orf95 locus has been associated with phosphorylated tau levels in cerebrospinal fluid and with ventricular volume.

    “the C16orf95 locus has been associated with phosphorylated tau levels in cerebrospinal fluid as well as with ventricular volume (Supplementary Note)11,12.”

    From Consensus meta-analysis of genome-wide association studies for Alzheimer’s disease and related dementias (2026) · cites this paper as [12]

    Table 1 (Results, Genome-wide association results; page not provided) identifies a ventricular-volume-associated variant at 16q24.2 annotated to FOXL1 and C16orf95. The Discussion associates cerebrospinal-fluid tau/phosphorylated tau with a different locus, 3q28, and does not establish that association for C16orf95. (LLM, conf=0.88)

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Authors
Vojinovic, D., Adams, H. H., Jian, X., Yang, Q., Smith, A. V., Bis, J. C., Teumer, A., Scholz, M., Armstrong, N. J., Hofer, E., Saba, Y., Luciano, M., Bernard, M., Trompet, S., Yang, J., Gillespie, N. A., van der Lee, S. J., Neumann, A., Ahmad, S., Andreassen, O. A., Ames, D., Amin, N., Arfanakis, K., Bastin, M. E., Becker, D. M., Beiser, A. S., Beyer, F., Brodaty, H., Bryan, R. N., Bülow, R., Dale, A. M., De Jager, P. L., Deary, I. J., DeCarli, C., Fleischman, D. A., Gottesman, R. F., van der Grond, J., Gudnason, V., Harris, T. B., Homuth, G., Knopman, D. S., Kwok, J. B., Lewis, C. E., Li, S., Loeffler, M., Lopez, O. L., Maillard, P., El Marroun, H., Mather, K. A., Mosley, T. H., Muetzel, R. L., Nauck, M., Nyquist, P. A., Panizzon, M. S., Pausova, Z., Psaty, B. M., Rice, K., Rotter, J. I., Royle, N., Satizabal, C. L., Schmidt, R., Schofield, P. R., Schreiner, P. J., Sidney, S., Stott, D. J., Thalamuthu, A., Uitterlinden, A. G., Valdés Hernández, M. C., Vernooij, M. W., Wen, W., White, T., Witte, A. V., Wittfeld, K., Wright, M. J., Yanek, L. R., Tiemeier, H., Kremen, W. S., Bennett, D. A., Jukema, J. W., Paus, T., Wardlaw, J. M., Schmidt, H., Sachdev, P. S., Villringer, A., Grabe, H. J., Longstreth, W. T., van Duijn, C. M., Launer, L. J., Seshadri, S., Ikram, M. A., & Fornage, M.
Affiliations
  • Erasmus MC (NL)
  • The University of Texas Health Science Center at Houston (US)
  • Boston University (US)
  • University of Iceland (IS)
  • University of Washington (US)
  • Universitätsmedizin Greifswald (DE)
  • Leipzig University (DE)
  • Murdoch University (AU)
  • Medical University of Graz (AT)
  • University of Graz (AT)
  • Hospital for Sick Children (CA)
  • Leiden University Medical Center (NL)
  • Rush University Medical Center (US)
  • Virginia Commonwealth University (US)
  • University of Oslo (NO)
  • The University of Melbourne (AU)
  • University of Edinburgh (GB)
  • Johns Hopkins University (US)
  • Max Planck Institute for Human Cognitive and Brain Sciences (DE)
  • UNSW Sydney (AU)
  • The University of Texas at Austin (US)
  • University of California San Diego (US)
  • University of California, Davis (US)
  • National Institutes of Health (US)
  • Mayo Clinic (US)
  • The University of Sydney (AU)
  • University of Alabama at Birmingham (US)
  • University of Mississippi Medical Center (US)
  • Kaiser Permanente Washington Health Research Institute (US)
  • The Lundquist Institute (US)
  • University of Minnesota (US)
  • Kaiser Permanente (US)
  • University of Glasgow (GB)
  • German Center for Neurodegenerative Diseases (DE)
  • The University of Queensland (AU)
Corresponding author
Fornage, Myriam
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-09-26
Volume
9
Issue
1
Pages
3945-3945
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-06234-w
PMC
PMC6158214
OpenAlex
W2890927800
Cited by
52
References
7
Citations by year
2026: 3 · 2025: 11 · 2024: 9 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 5
FWCI
0.72
Type
journal article
Language
en
Open access
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Funders
  • National Institutes of Health (1r01hl120393-01a1, 5u01hl096899-08, 5u01hl096902-08)
  • University of California, San Diego
  • Medical Research Council (MR/K026992/1, MR/M013111/1)
  • Biotechnology and Biological Sciences Research Council (BB/F019394/1)
  • National Institute on Aging (R01AG017917, P30AG010129, U01AG049505, U01AG052409, R01AG015819, P30AG010161, R01AG054076)
  • National Heart, Lung, and Blood Institute (R01-HL120393, U01HL130114, U01HL120393, U01-HL-096899, U01-HL-096902, R01HL105756, U01HL096917, U01HL096812)
  • National Institute of Neurological Disorders and Stroke (R01NS087541, R01NS017950)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
Keywords
lateral ventricle volume, brain ventricles, genetic loci, brain structure, thalamus, tau pathology, S1P signaling, cytoskeletal organization, genetic overlap, brain aging, heritability
MeSH terms
Aged, Humans, Middle Aged, Organ Size, Genome, Human, Lateral Ventricles, Genome-Wide Association Study

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