Gray matter heritability in family-based and population-based studies using voxel-based morphometry

Gray matter heritability in family-based and population-based studies using voxel-based morphometry

van der Lee, Sven J. (Erasmus MC)
Roshchupkin, Gennady V. (Erasmus MC)
Adams, Hieab H. (Erasmus MC)
Schmidt, Helena (Medical University Graz)
Hofer, Edith (Medical University Graz)
Saba, Yasaman (Medical University Graz)
Schmidt, Reinhold (Medical University Graz)
Hofman, Albert (Erasmus MC)
Amin, Najaf (Erasmus MC)
van Duijn, Cornelia M. (Erasmus MC)
Vernooij, Meike W. (Erasmus MC)
Ikram, M. Arfan (Erasmus MC)
Niessen, W.J. (TU Delft ImPhys/Quantitative Imaging; Erasmus MC)

2017-05-01

Background: 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). Methods: 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. Results: 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. Conclusion: 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.

brain structure heritability
family-based study
genetics
gray matter
magnetic resonance imaging
population-based study
voxel-based morphometry
grey matter

http://resolver.tudelft.nl/uuid:51544de7-fc2b-4ebb-933a-ec636f06eea7

https://doi.org/10.1002/hbm.23528

2018-02-01

1065-9471

Human Brain Mapping, 38 (5), 2408-2423

Institutional Repository

journal article

© 2017 Sven J. van der Lee, Gennady V. Roshchupkin, Hieab H. Adams, Helena Schmidt, Edith Hofer, Yasaman Saba, Reinhold Schmidt, Albert Hofman, Najaf Amin, Cornelia M. van Duijn, Meike W. Vernooij, M. Arfan Ikram, W.J. Niessen