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

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.

SUBMITTER: Vojinovic D 

PROVIDER: S-EPMC6158214 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Vojinovic Dina D   Adams Hieab H HH   Jian Xueqiu X   Yang Qiong Q   Smith Albert Vernon AV   Bis Joshua C JC   Teumer Alexander A   Scholz Markus M   Armstrong Nicola J NJ   Hofer Edith E   Saba Yasaman Y   Luciano Michelle M   Bernard Manon M   Trompet Stella S   Yang Jingyun J   Gillespie Nathan A NA   van der Lee Sven J SJ   Neumann Alexander A   Ahmad Shahzad S   Andreassen Ole A OA   Ames David D   Amin Najaf N   Arfanakis Konstantinos K   Bastin Mark E ME   Becker Diane M DM   Beiser Alexa S AS   Beyer Frauke F   Brodaty Henry H   Bryan R Nick RN   Bülow Robin R   Dale Anders M AM   De Jager Philip L PL   Deary Ian J IJ   DeCarli Charles C   Fleischman Debra A DA   Gottesman Rebecca F RF   van der Grond Jeroen J   Gudnason Vilmundur V   Harris Tamara B TB   Homuth Georg G   Knopman David S DS   Kwok John B JB   Lewis Cora E CE   Li Shuo S   Loeffler Markus M   Lopez Oscar L OL   Maillard Pauline P   El Marroun Hanan H   Mather Karen A KA   Mosley Thomas H TH   Muetzel Ryan L RL   Nauck Matthias M   Nyquist Paul A PA   Panizzon Matthew S MS   Pausova Zdenka Z   Psaty Bruce M BM   Rice Ken K   Rotter Jerome I JI   Royle Natalie N   Satizabal Claudia L CL   Schmidt Reinhold R   Schofield Peter R PR   Schreiner Pamela J PJ   Sidney Stephen S   Stott David J DJ   Thalamuthu Anbupalam A   Uitterlinden Andre G AG   Valdés Hernández Maria C MC   Vernooij Meike W MW   Wen Wei W   White Tonya T   Witte A Veronica AV   Wittfeld Katharina K   Wright Margaret J MJ   Yanek Lisa R LR   Tiemeier Henning H   Kremen William S WS   Bennett David A DA   Jukema J Wouter JW   Paus Tomas T   Wardlaw Joanna M JM   Schmidt Helena H   Sachdev Perminder S PS   Villringer Arno A   Grabe Hans Jörgen HJ   Longstreth W T WT   van Duijn Cornelia M CM   Launer Lenore J LJ   Seshadri Sudha S   Ikram M Arfan MA   Fornage Myriam M  

Nature communications 20180926 1

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 chrom  ...[more]

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