A genome-wide pathway enrichment analysis identifies brain region related biological pathways associated with intelligence

Intelligence is an important quantitative trait associated with human cognitive ability. The genetic basis of intelligence remains unclear now. Utilizing the latest chromosomal enhancer maps of brain regions, we explored brain region related biological pathways associated with intelligence. Summary data was derived from a large scale genome-wide association study (GWAS) of human, involving 78,308 unrelated individuals from 13 cohorts. The chromosomal enhancer maps of 8 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for intelligence. Gene set enrichment analysis was then conducted to identify the biological pathways associated with intelligence for 8 brain regions, respectively. A total of 178 KEGG pathways was analyzed in this study. We detected multiple biological pathways showing cross brain regions or brain region specific association signals for human intelligence. For instance, KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS pathway presented association signals for intelligence across 8 brain regions (all P value < 0.01). KEGG_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIO_SERIES was detected for 5 brain regions. We also identified several brain region specific pathways, such as AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR_METABOLISM for Germinal Matrix (P value = 0.009) and FRUCTOSE_AND_MANNOSE_METABOLISM for Anterior Caudate (P value = 0.005). Our study results provided novel clues for understanding the genetic mechanism of intelligence.