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

Dina Vojinovic; Hieab Adams; XQ Jian; Q Yang; AV Smith; JC Bis; A Teumer; M Scholz; NJ Armstrong; E Hofer; Y Saba; M Luciano; M Bernard; S Trompet; JY Yang; NA Gillespie; Sven van der Lee; Alexander Neumann; Shahzad Ahmad; OA Andreassen; D Ames; Najaf Amin; K Arfanakis; ME Bastin; DM Becker; AS Beiser; F Beyer; H Brodaty; RN Bryan; R Bulow; AM Dale; PL De Jager; IJ Deary; C DeCarli; DA Fleischman; RF Gottesman; J van der Grond; V Gudnason; TB Harris; G Homuth; DS Knopman; JB Kwok; CE Lewis; S Li; M Loeffler; OL Lopez; P Maillard; Hanan El Marroun; KA Mather; TH Mosley; Ryan Muetzel; M Nauck; PA Nyquist; MS Panizzon; Z Pausova; BM Psaty; K Rice; JI Rotter; N Royle; CL Satizabal; R Schmidt; PR Schofield; PJ Schreiner; S Sidney; DJ Stott; A Thalamuthu; André Uitterlinden; MCV Hernandez; Meike Vernooij; W Wen; Tonya White; AV Witte; K Wittfeld; MJ Wright; LR Yanek; Henning Tiemeier; WS Kremen; DA Bennett; JW Jukema; T Paus; JM Wardlaw; H Schmidt; PS Sachdev; A Villringer; HJ Grabe; WT Longstreth; Cornelia Duijn; LJ Launer; S Seshadri; Arfan Ikram; M Fornage

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, Hieab Adams, XQ Jian, Q Yang, AV Smith, JC Bis, A Teumer, M Scholz, NJ Armstrong, E Hofer, Y Saba, M Luciano, M Bernard, S Trompet, JY Yang, NA Gillespie, Sven van der Lee, Alexander Neumann, Shahzad Ahmad, OA AndreassenD Ames, Najaf Amin, K Arfanakis, ME Bastin, DM Becker, AS Beiser, F Beyer, H Brodaty, RN Bryan, R Bulow, AM Dale, PL De Jager, IJ Deary, C DeCarli, DA Fleischman, RF Gottesman, J van der Grond, V Gudnason, TB Harris, G Homuth, DS Knopman, JB Kwok, CE Lewis, S Li, M Loeffler, OL Lopez, P Maillard, Hanan El Marroun, KA Mather, TH Mosley, Ryan Muetzel, M Nauck, PA Nyquist, MS Panizzon, Z Pausova, BM Psaty, K Rice, JI Rotter, N Royle, CL Satizabal, R Schmidt, PR Schofield, PJ Schreiner, S Sidney, DJ Stott, A Thalamuthu, André Uitterlinden, MCV Hernandez, Meike Vernooij, W Wen, Tonya White, AV Witte, K Wittfeld, MJ Wright, LR Yanek, Henning Tiemeier, WS Kremen, DA Bennett, JW Jukema, T Paus, JM Wardlaw, H Schmidt, PS Sachdev, A Villringer, HJ Grabe, WT Longstreth, Cornelia Duijn, LJ Launer, S Seshadri, Arfan Ikram, M Fornage

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Abstract

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 (?genetic?=?-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

Original language	English
Article number	3945
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06234-w
Publication status	Published - 2018

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Vojinovic, D., Adams, H., Jian, XQ., Yang, Q., Smith, AV., Bis, JC., Teumer, A., Scholz, M., Armstrong, NJ., Hofer, E., Saba, Y., Luciano, M., Bernard, M., Trompet, S., Yang, JY., Gillespie, NA., van der Lee, S., Neumann, A., Ahmad, S., ... Fornage, M. (2018). Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume. Nature Communications, 9(1), [3945]. https://doi.org/10.1038/s41467-018-06234-w

@article{b975655f808b4c80931372920fb15dfe,

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

abstract = "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 (?genetic?=?-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",

author = "Dina Vojinovic and Hieab Adams and XQ Jian and Q Yang and AV Smith and JC Bis and A Teumer and M Scholz and NJ Armstrong and E Hofer and Y Saba and M Luciano and M Bernard and S Trompet and JY Yang and NA Gillespie and {van der Lee}, Sven and Alexander Neumann and Shahzad Ahmad and OA Andreassen and D Ames and Najaf Amin and K Arfanakis and ME Bastin and DM Becker and AS Beiser and F Beyer and H Brodaty and RN Bryan and R Bulow and AM Dale and {De Jager}, PL and IJ Deary and C DeCarli and DA Fleischman and RF Gottesman and {van der Grond}, J and V Gudnason and TB Harris and G Homuth and DS Knopman and JB Kwok and CE Lewis and S Li and M Loeffler and OL Lopez and P Maillard and {El Marroun}, Hanan and KA Mather and TH Mosley and Ryan Muetzel and M Nauck and PA Nyquist and MS Panizzon and Z Pausova and BM Psaty and K Rice and JI Rotter and N Royle and CL Satizabal and R Schmidt and PR Schofield and PJ Schreiner and S Sidney and DJ Stott and A Thalamuthu and Andr{\'e} Uitterlinden and MCV Hernandez and Meike Vernooij and W Wen and Tonya White and AV Witte and K Wittfeld and MJ Wright and LR Yanek and Henning Tiemeier and WS Kremen and DA Bennett and JW Jukema and T Paus and JM Wardlaw and H Schmidt and PS Sachdev and A Villringer and HJ Grabe and WT Longstreth and Cornelia Duijn and LJ Launer and S Seshadri and Arfan Ikram and M Fornage",

year = "2018",

doi = "10.1038/s41467-018-06234-w",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Vojinovic, D, Adams, H, Jian, XQ, Yang, Q, Smith, AV, Bis, JC, Teumer, A, Scholz, M, Armstrong, NJ, Hofer, E, Saba, Y, Luciano, M, Bernard, M, Trompet, S, Yang, JY, Gillespie, NA, van der Lee, S, Neumann, A , Ahmad, S, Andreassen, OA, Ames, D, Amin, N, Arfanakis, K, Bastin, ME, Becker, DM, Beiser, AS, Beyer, F, Brodaty, H, Bryan, RN, Bulow, R, Dale, AM, De Jager, PL, Deary, IJ, DeCarli, C, Fleischman, DA, Gottesman, RF, van der Grond, J, Gudnason, V, Harris, TB, Homuth, G, Knopman, DS, Kwok, JB, Lewis, CE, Li, S, Loeffler, M, Lopez, OL, Maillard, P, El Marroun, H, Mather, KA, Mosley, TH, Muetzel, R, Nauck, M, Nyquist, PA, Panizzon, MS, Pausova, Z, Psaty, BM, Rice, K, Rotter, JI, Royle, N, Satizabal, CL, Schmidt, R, Schofield, PR, Schreiner, PJ, Sidney, S, Stott, DJ, Thalamuthu, A, Uitterlinden, A, Hernandez, MCV, Vernooij, M, Wen, W, White, T, Witte, AV, Wittfeld, K, Wright, MJ, Yanek, LR, Tiemeier, H, Kremen, WS, Bennett, DA, Jukema, JW, Paus, T, Wardlaw, JM, Schmidt, H, Sachdev, PS, Villringer, A, Grabe, HJ, Longstreth, WT, Duijn, C, Launer, LJ, Seshadri, S, Ikram, A & Fornage, M 2018, 'Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume', Nature Communications, vol. 9, no. 1, 3945. https://doi.org/10.1038/s41467-018-06234-w

TY - JOUR

T1 - Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

AU - Vojinovic, Dina

AU - Adams, Hieab

AU - Jian, XQ

AU - Yang, Q

AU - Smith, AV

AU - Bis, JC

AU - Teumer, A

AU - Scholz, M

AU - Armstrong, NJ

AU - Hofer, E

AU - Saba, Y

AU - Luciano, M

AU - Bernard, M

AU - Trompet, S

AU - Yang, JY

AU - Gillespie, NA

AU - van der Lee, Sven

AU - Neumann, Alexander

AU - Ahmad, Shahzad

AU - Andreassen, OA

AU - Ames, D

AU - Amin, Najaf

AU - Arfanakis, K

AU - Bastin, ME

AU - Becker, DM

AU - Beiser, AS

AU - Beyer, F

AU - Brodaty, H

AU - Bryan, RN

AU - Bulow, R

AU - Dale, AM

AU - De Jager, PL

AU - Deary, IJ

AU - DeCarli, C

AU - Fleischman, DA

AU - Gottesman, RF

AU - van der Grond, J

AU - Gudnason, V

AU - Harris, TB

AU - Homuth, G

AU - Knopman, DS

AU - Kwok, JB

AU - Lewis, CE

AU - Li, S

AU - Loeffler, M

AU - Lopez, OL

AU - Maillard, P

AU - El Marroun, Hanan

AU - Mather, KA

AU - Mosley, TH

AU - Muetzel, Ryan

AU - Nauck, M

AU - Nyquist, PA

AU - Panizzon, MS

AU - Pausova, Z

AU - Psaty, BM

AU - Rice, K

AU - Rotter, JI

AU - Royle, N

AU - Satizabal, CL

AU - Schmidt, R

AU - Schofield, PR

AU - Schreiner, PJ

AU - Sidney, S

AU - Stott, DJ

AU - Thalamuthu, A

AU - Uitterlinden, André

AU - Hernandez, MCV

AU - Vernooij, Meike

AU - Wen, W

AU - White, Tonya

AU - Witte, AV

AU - Wittfeld, K

AU - Wright, MJ

AU - Yanek, LR

AU - Tiemeier, Henning

AU - Kremen, WS

AU - Bennett, DA

AU - Jukema, JW

AU - Paus, T

AU - Wardlaw, JM

AU - Schmidt, H

AU - Sachdev, PS

AU - Villringer, A

AU - Grabe, HJ

AU - Longstreth, WT

AU - Duijn, Cornelia

AU - Launer, LJ

AU - Seshadri, S

AU - Ikram, Arfan

AU - Fornage, M

PY - 2018

Y1 - 2018

N2 - 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 (?genetic?=?-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

AB - 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 (?genetic?=?-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

UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158214/pdf/41467_2018_Article_6234.pdf

U2 - 10.1038/s41467-018-06234-w

DO - 10.1038/s41467-018-06234-w

M3 - Article

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3945

ER -

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

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