The brain is a complex structure whose blueprint is archived in our genes. It is still quite unknown how genes influence the processes that shape our brain. An international research consortium has now discovered five candidate genes which are associated with the size of various brain regions. The researchers hope that these results will help them reach a better understanding of the molecular principles of mental disorders. The study was published in the renowned science journal "Nature" on January 21, 2015.

The international research consortium ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) has conducted a large-scale study on how genetic variants influence the grey matter volumes of various brain regions. The scientists evaluated the brain scans of a total of 30,717 people coming from 50 cohort studies all over the world, also from the integrated genome research network MooDS funded by the German Ministry of Education and Research. The images provided the basis for determining the intracranial volume and seven different brain regions.

What genes are responsible for the varying dimensions of brain structures among humans? To find an answer to this question, the researchers compared the brain-scan data with gene analyses and found a total of five new genetic variants located at the sites DLG2 (seated on chromosome 11), FAT3 (chromosome 11), KTN1 (chromosome 14), DCC (chromosome 18), and BCL2L1 (chromosome 20) which are connected with the volume of the brain structures known as "putamen" and "caudate nucleus".

These brain structures belong to the so-called subcortical core regions of the cerebrum. They are involved in central relay functions of nerve tracts inside the brain. The biological details telling us just how the identified genes exert an influence on the dimensions of the brain structures still remain unknown. There are indications, for example, revealing that the migration of nerve cells (DCC) or the programmed cell death of immature neurons (BCL2L1) are altered in the growing brain.

The role of the KTN1 gene
KTN1 produced the strongest effect of all the genes studied so far. As yet, hardly anything is known about the function of this gene in the development of nerve cells. Further studies could reveal that this genetic variant affects gene transcription and thus most likely also the number of copies of synthetized protein.

A better understanding of what causes brain alterations in serious psychiatric disorders might reveal approaches to new therapy options. Research into the genetic interactions and reductions of gray matter in patients with schizophrenia is pioneering in this regard and someday might also give us the option to intervene at an early stage, which means when patients are in their childhood or adolescence, explains Prof. Dr. Stefan Ehrlich, Director of the Department of Applied Developmental Neurosciences at the Clinic and Policlinic for Pediatric Psychiatry and Psychotherapy of the Carl Gustav Carus University Hospital in Dresden and Coordinator of the MCIC Network.

Reference: Common genetic variants influence human subcortical brain structures, Nature, DOI: 10.1038/nature14101

Information for Journalists:

Department of Child and Adolescent Psychiatry
Translational Developmental Neuroscience Section
Faculty of Medicine & University Hospital C. G. Carus

Technische Universität Dresden

Prof. Stefan Ehrlich, Deputy Chief Consultant
Fon: +49 (0)351 458-2244

Fax: +49 (0)351 458-5754


www.uniklinikum-dresden.de 
www.transdenlab.de