Common genetic variants influence human subcortical brain structures

Authors

Derrek P. Hibar
Jason L. Stein
Miguel E. Renteria
Alejandro Arias-Vasquez
John Blangero, The University of Texas Rio Grande ValleyFollow
Anderson M. Winkler, The University of Texas Rio Grande ValleyFollow
Joanne E. Curran, The University of Texas Rio Grande Valley
Thomas D. Dyer, The University of Texas Rio Grande Valley
Peter T. Fox
Ravi Duggirala, The University of Texas Rio Grande Valley

Document Type

Article

Publication Date

4-9-2015

Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Comments

Original published version available at https://doi.org/10.1038/nature14101

Recommended Citation

Hibar, D. P., Stein, J. L., Renteria, M. E., Arias-Vasquez, A., Desrivières, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B. S., Armstrong, N. J., Bernard, M., Bohlken, M. M., Boks, M. P., Bralten, J., Brown, A. A., Chakravarty, M. M., Chen, Q., Ching, C. R., … Medland, S. E. (2015). Common genetic variants influence human subcortical brain structures. Nature, 520(7546), 224–229. https://doi.org/10.1038/nature14101

First Page

224

Last Page

9

Publication Title

Nature

DOI

10.1038/nature14101

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics