Brain imaging genomics: influences of genomic variability on the structure and function of the human brain

Abstract

Abstract Brain imaging genomics is an emerging discipline in which genomic and brain imaging data are integrated in order to elucidate the molecular mechanisms that underly brain phenotypes and diseases, including neuropsychiatric disorders. As with all genetic analyses of complex traits and diseases, brain imaging genomics has evolved from small, individual candidate gene investigations towards large, collaborative genome-wide association studies. Recent investigations, mostly population-based, have studied well-powered cohorts comprising tens of thousands of individuals and identified multiple robust associations of single-nucleotide polymorphisms and copy number variants with structural and functional brain phenotypes. Such systematic genomic screens of millions of genetic variants have generated initial insights into the genetic architecture of brain phenotypes and demonstrated that their etiology is polygenic in nature, involving multiple common variants with small effect sizes and rare variants with larger effect sizes. Ongoing international collaborative initiatives are now working to obtain a more complete picture of the underlying biology. As in other complex phenotypes, novel approaches – such as gene–gene interaction, gene–environment interaction, and epigenetic analyses – are being implemented in order to investigate their contribution to the observed phenotypic variability. An important consideration for future research will be the translation of brain imaging genomics findings into clinical practice.