Abstract
In T 1 -weighted magnetic resonance imaging (MRI), cortical thickness (CT) and gray-white matter contrast (GWC) capture brain morphological traits and vary with age-related disease. To gain insight into genetic factors underlying brain structure and dynamics observed during neurodegeneration, this genome-wide association study (GWAS) quantifies the relationship between single nucleotide polymorphisms (SNPs) and both CT and GWC in UK Biobank participants ( N = 43,002). To our knowledge, this is the first GWAS to investigate the genetic determinants of cortical T 1 -MRI GWC in humans. We found 251 SNPs associated with CT or GWC for at least 1% of cortical locations, including 42 for both CT and GWC; 127 for only CT; and 82 for only GWC. Identified SNPs include rs1080066 (THSB1, featuring the strongest association with both CT and GWC), rs13107325 (SLC39A8, linked to CT at the largest number of cortical locations), and rs864736 (KCNK2, associated with GWC at the largest number of cortical locations). Dimensionality reduction reveals three major gene ontologies constraining CT (neural signaling, ion transport, cell migration) and four constraining GWC (neural cell development, cellular homeostasis, tissue repair, ion transport). Our findings provide insight into genetic determinants of GWC and CT, highlighting pathways associated with brain anatomy and dynamics of neurodegeneration. These insights can assist the development of gene therapies and treatments targeting brain diseases.