Integrating genome-wide association study, chromosomal enhancer maps and element-gene interaction networks detected brain regions related associations between elements and ADHD/IQ

Abstract

Objective: To explore the associations between chemical elements and attention deficit hyperactivity disorder (ADHD)/intelligence quotient (IQ).

Methods: We applied elements related gene set enrichment analysis (ERGSEA) to explore the relationships between elements and ADHD/IQ. The GWAS dataset of ADHD was derived from the Psychiatric Genomics Consortium, involving 55,374 individuals. The GWAS dataset of IQ was derived from UK Biobank web-based measure (n = 17,862), UK Biobank touchscreen measure (n = 36,257), CHIC consortium (n = 12,441) and five additional cohorts (n = 11,748). Enhancer-gene datasets of eight brain tissues consist of 935 individuals. Utilizing the published GWAS summary and eight brain region-related chromosomal enhancer maps to obtain the SNP association testing signals. The element-gene interaction datasets of 21 elements were downloaded from the comparative toxicogenomics database (CTD).

Results: ERGSEA observed significant associations between 4 elements and ADHD, such as Al at Hippocampus Middle (P value = 0.040), As at Angular Gyrus (P value = 0.007) and Na at Hippocampus Middle (P value = 0.026). Additionally, ERGSEA identified that 5 elements were associated with IQ, mainly including Al at Dorsolateral Prefrontal Cortex (P value = 0.017), As at Dorsolateral Prefrontal Cortex (P value = 0.004) and Pb at Germinal Matrix (P value = 0.045).

Conclusion: Our study results provide novel clues for understanding the associations between elements and ADHD/IQ. This study also illustrated the good performance of ERGSEA approach for complex diseases.

Keywords: Attention deficit hyperactivity disorder; Element related gene set enrichment analysis; Enhancer; Genome-wide association studies; Intelligence quotient.