Trans-ancestral genome-wide association studies of brain imaging phenotypes

Abstract Genome-wide association studies of brain imaging phenotypes are mainly performed in European populations, but other populations are severely under-represented. Here, we conducted Chinese-alone and trans-ancestral genome-wide association studies of 3,414 brain imaging phenotypes in 7,058 Chinese and 33,224 European individuals. We identified 37 novel variant-phenotype associations in Chinese-alone analyses and 459 additional novel associations in trans-ancestral meta-analyses under the thresholds of P < 1.46 × 10− 11 for discovery and P < 0.05 for replication. We pooled genome-wide significant associations for brain imaging phenotypes identified in either single-ancestral or trans-ancestral analyses into 6,361 independent significant associations. These associations were unevenly distributed in the genome and across the brain phenotypic subgroups and demonstrated significant enrichment for nervous system development and signal transduction. We further categorized the 4,890 pooled genome-wide significant associations whose index variants were included in both Chinese and European analyses into 43 ancestry-specific and 3,524 ancestry-shared associations. Loci of the 6,361 pooled genome-wide significant associations for brain imaging phenotypes were shared by 16 brain-related non-imaging traits including cognition, personality, risk behavior, addiction, and neuropsychiatric disorders. Our results provide a valuable catalog of genetic associations for brain imaging phenotypes in diverse populations.