title: TMEM106B influences volume of left-sided temporal lobe and interhemispheric structures in the general population.
abstract: BACKGROUND
  Frontotemporal lobar degeneration is a neurodegenerative disease characterized by brain atrophy of the frontal and anterior temporal lobes. The associated frontotemporal dementia syndromes are clinically heterogeneous, and the pattern of affected cortical regions varies among subtypes. The TMEM106B rs1990622 polymorphism is associated with frontotemporal lobar degeneration, but little is known about how it affects the brain.
  
  
  METHODS
  We investigated the rs1990622 polymorphism in relation to regional brain volumes to identify potential structures through which TMEM106B confers risk for frontotemporal lobar degeneration. In 4413 nondemented and stroke-free participants from the population-based Rotterdam Study, 150 cortical brain structures and 6 commissural regions were segmented from magnetic resonance imaging.
  
  
  RESULTS
  A distinct pattern of association was found between rs1990622 and gray matter volume of left-sided temporal brain regions important for language processing, including the superior temporal gyrus (β=-88.8 μL per risk allele, p=7.64×10(-5)), which contains Wernicke's area. The risk allele was also associated with a smaller anterior commissure cross-sectional area (β=-.167 mm2 per risk allele, p=4.90×10(-5)) and posterior part of the corpus callosum (β=-15.3 μL per risk allele, p=1.23×10(-5)), both of which contain temporal lobe commissural tracts.
  
  
  CONCLUSIONS
  The asymmetric, predominantly left-sided involvement suggests an effect of TMEM106B on functions lateralized to the dominant hemisphere, such as language. These results show that, in nondemented persons, TMEM106B influences the volume of temporal brain regions that are important for language processing.
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Hieab H H
authors.initials: HH
authors.lastname: Adams
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Benjamin F J
authors.initials: BF
authors.lastname: Verhaaren
authors.affiliation: Department of Radiology, Erasmus MC, Rotterdam, the Netherlands; Department of Medical Informatics, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Henri A
authors.initials: HA
authors.lastname: Vrooman
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: Department of Medical Informatics, Erasmus MC, Rotterdam, the Netherlands; Faculty of Applied Sciences, Delft University, Delft, The Netherlands.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, Rotterdam, the Netherlands. Electronic address: m.a.ikram@erasmusmc.nl.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
mesh_terms: D000368:Aged; D001921:Brain / Q000033:anatomy & histology*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics; D007839:Functional Laterality / Q000235:genetics; D020022:Genetic Predisposition to Disease; D066128:Gray Matter / Q000033:anatomy & histology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013702:Temporal Lobe / Q000033:anatomy & histology*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C556915:TMEM106B protein, human
keywords: Brain volumetry; commissural tracts; frontotemporal lobar degeneration; genetics; magnetic resonance imaging; population-based