Multivariate genome-wide association study identifies 1735 unique genetic loci associated with cortical morphology.

Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we exploit the distributed nature of genetic effects across the brain and apply the Multivariate Omnibus Statistical Test (MOSTest) to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) measures from N=35,657 participants in the UK Biobank. We identified 1598 loci for cortical surface area and 1054 for cortical thickness, reflecting an approximate 10-fold increase compared to the most recent report using commonly applied GWAS methods. Our power analysis indicates that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional GWAS approaches. Our gene-based analyses implicate 10% of all protein-coding genes and point towards pathways involved in neurogenesis and cell differentiation, supporting that we are capturing valid biological mechanisms underlying brain anatomy.