title: Gray matter heritability in family-based and population-based studies using voxel-based morphometry.
abstract: The combination of genetics and imaging has improved their understanding of the brain through studies of aggregate measures obtained from high-resolution structural imaging. Voxel-wise analyses have the potential to provide more detailed information of genetic influences on the brain. Here they report a large-scale study of the heritability of gray matter at voxel resolution (1 × 1 × 1 mm).
  
  
  
  Validated voxel-based morphometry (VBM) protocols were applied to process magnetic resonance imaging data of 3,239 unrelated subjects from a population-based study and 491 subjects from two family-based studies. Genome-wide genetic data was used to estimate voxel-wise gray matter heritability of the unrelated subjects and pedigree-structure was used to estimate heritability in families. They subsequently associated two genetic variants, known to be linked with subcortical brain volume, with most heritable voxels to determine if this would enhance their association signals.
  
  
  
  Voxels significantly heritable in both estimates mapped to subcortical structures, but also voxels in the language areas of the left hemisphere were found significantly heritable. When comparing regional patterns of heritability, family-based estimates were higher than population-based estimates. However, regional consistency of the heritability measures across study designs was high (Pearson's correlation coefficient = 0.73, P = 2.6 × 10-13). They further show enhancement of the association signal of two previously discovered genetic loci with subcortical volume by using only the most heritable voxels.
  
  
  
  Gray matter voxel-wise heritability can be reliably estimated with different methods. Combining heritability estimates from multiple studies is feasible to construct reliable heritability maps of gray matter voxels. Hum Brain Mapp 38:2408-2423, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Sven J
authors.initials: SJ
authors.lastname: van der Lee
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Gennady V
authors.initials: GV
authors.lastname: Roshchupkin
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Hieab H H
authors.initials: HH
authors.lastname: Adams
authors.affiliation: Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.|Department of Neurology, Medical University Graz, Graz, Austria.
authors.forename: Helena
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Graz, Austria.|Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, Austria.
authors.forename: Edith
authors.initials: E
authors.lastname: Hofer
authors.affiliation: Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Saba
authors.affiliation: Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Graz, Austria.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Najaf
authors.initials: N
authors.lastname: Amin
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.|Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D001931:Brain Mapping; D015331:Cohort Studies; D018672:Community Health Planning; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009426:Netherlands
keywords: brain structure heritability; family-based study; genetics; gray matter; magnetic resonance imaging; population-based study; voxel-based morphometry