Healthy functioning of the human brain relies on its highly intricate structure, which is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate cognitive, emotional and motor abilities. At the individual level, genetic variations exert lasting influences on brain structures and functions. Yet, although measures of brain structure are heritable, little is known about the detailed mechanisms through which brain architecture is built, and how molecular and cellular processes are translated into complex cognitive and behavioural characteristics.

We have started to address this, conducting collaborative large-scale genetic analysis of magnetic resonance imaging (MRI) scans within the context of two international neuroimaging Consortia, IMAGEN and the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium to identify genetic factors accounting for inter-individual differences in brain structure and their impact on cognition. These enabled key findings. First, they allowed us to identify the first gene linking cortical thickness to cognitive abilities in adolescents. They also enabled us to conduct the first genome-wide association studies (GWAS) of the volumes of seven subcortical regions and intracranial volume, derived from MRIs of 29,037 individuals, leading to the identification of six novel genetic variants influencing the volumes of the putamen, caudate nucleus, hippocampus and intracranial volume.

Nonetheless, more refined methodologies than classical GWAS, taking into consideration developmental and environmental aspects and the polygenic nature of brain measures promise to broaden our understanding of the functional impact of brain-relevant genetic variations on behaviour and disease. We are also extending our genetic analyses of brain measures and have set up the ENIGMA Epigenetics Working Group, with the goal to begin to understand how epigenetic mechanisms contribute to brain development and disease.

I will describe results from these imaging genomics studies and discuss their emerging significance for neuropsychiatry.

Recent publications:

1. Neural basis of reward anticipation and its genetic determinants. PNAS, 2016.

2. Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents. Mol Psychiatry. 2015

3. Common genetic variants influence human subcortical brain structures. Nature. 2015