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. 2018 Sep 26;9(1):3945.
doi: 10.1038/s41467-018-06234-w.

Genome-wide Association Study of 23,500 Individuals Identifies 7 Loci Associated With Brain Ventricular Volume

Dina Vojinovic  1 Hieab H Adams  2   3 Xueqiu Jian  4 Qiong Yang  5 Albert Vernon Smith  6   7 Joshua C Bis  8 Alexander Teumer  9 Markus Scholz  10   11 Nicola J Armstrong  12   13 Edith Hofer  14   15 Yasaman Saba  16 Michelle Luciano  17 Manon Bernard  18 Stella Trompet  19   20 Jingyun Yang  21   22 Nathan A Gillespie  23 Sven J van der Lee  2 Alexander Neumann  24 Shahzad Ahmad  2 Ole A Andreassen  25 David Ames  26   27 Najaf Amin  2 Konstantinos Arfanakis  21   28   29 Mark E Bastin  17   30   31 Diane M Becker  32 Alexa S Beiser  5 Frauke Beyer  33 Henry Brodaty  13   34 R Nick Bryan  35 Robin Bülow  36 Anders M Dale  37 Philip L De Jager  38   39 Ian J Deary  17 Charles DeCarli  40 Debra A Fleischman  21   22   41 Rebecca F Gottesman  42 Jeroen van der Grond  43 Vilmundur Gudnason  6   7 Tamara B Harris  44 Georg Homuth  45 David S Knopman  46 John B Kwok  47   48 Cora E Lewis  49 Shuo Li  5 Markus Loeffler  10   11 Oscar L Lopez  50 Pauline Maillard  40 Hanan El Marroun  24   51 Karen A Mather  13   52 Thomas H Mosley  53 Ryan L Muetzel  2   24 Matthias Nauck  54 Paul A Nyquist  42 Matthew S Panizzon  55 Zdenka Pausova  18   56 Bruce M Psaty  8   57   58   59 Ken Rice  60 Jerome I Rotter  61   62 Natalie Royle  17   30   31 Claudia L Satizabal  63   64 Reinhold Schmidt  14 Peter R Schofield  47   52 Pamela J Schreiner  65 Stephen Sidney  66 David J Stott  67 Anbupalam Thalamuthu  13 Andre G Uitterlinden  68 Maria C Valdés Hernández  17   30   31 Meike W Vernooij  2   3 Wei Wen  13 Tonya White  3   24 A Veronica Witte  33   69 Katharina Wittfeld  70 Margaret J Wright  71 Lisa R Yanek  32 Henning Tiemeier  24   72 William S Kremen  55 David A Bennett  21   22 J Wouter Jukema  20   73 Tomas Paus  74   75 Joanna M Wardlaw  17   30   31 Helena Schmidt  16 Perminder S Sachdev  13   76 Arno Villringer  33   69 Hans Jörgen Grabe  70   77 W T Longstreth  57   78 Cornelia M van Duijn  2   79 Lenore J Launer  44 Sudha Seshadri  63   64 M Arfan Ikram  2   3   80 Myriam Fornage  81
Free PMC article

Genome-wide Association Study of 23,500 Individuals Identifies 7 Loci Associated With Brain Ventricular Volume

Dina Vojinovic et al. Nat Commun. .
Free PMC article


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.

Conflict of interest statement

A.M.D. is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict of interest policies. The remaining authors declare no competing interests.


Fig. 1
Fig. 1
Manhattan plot for stage 3 genome-wide association meta-analysis. Each dot represents a variant. The plot shows –log10 p-values for all variants. Red line represents the genome-wide significance threshold (p-value < 5 × 10−8), whereas blue line denotes suggestive threshold (p-value < 1 × 10−5)
Fig. 2
Fig. 2
Regional association and recombination plots in combined stage 3 GWA meta-analysis. The left axis represents –log10 p-values for association with total later ventricular volume. The right axis represents the recombination rate, and the x-axis represents chromosomal position (hg19 genomic position). The most significant SNPs of the regions are denoted with a purple diamond. Surrounding SNPs are colored according to their pairwise correlation (r2) with the top-associated SNP of the region. The gene annotations are below the figure
Fig. 3
Fig. 3
Functional enrichment analysis of lateral ventricular volume loci within DNaseI hypersensitivity spots. The radial lines show fold enrichment (FE) at eight GWA p-value thresholds. The results are shown for each of 424 cell types which are sorted by tissue, represented along the outer circle of the plot. The font size is proportional to the number of cell types from the tissue. FE values are plotted with different colors with respect to different GWA thresholds. Significant enrichment for a given cell type is denoted along the outer circle of the plot from a GWA p-value threshold <10−5 (outermost) to GWA p-value threshold <10−8 (innermost). The results show ubiquitous enrichment

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