TTLL11 gene is associated with sustained attention performance and brain networks: A genome‐wide association study of a healthy Chinese sample

• Published in: Genes, brain and behavior brain and behavior, 2023-02, Vol.22 (1), p.e12835-n/a
• Main Authors: Liu, Hejun, Zhao, Xiaoyu, Xue, Gui, Chen, Chuansheng, Dong, Qi, Gao, Xuping, Yang, Li, Chen, Chunhui
• Format: Article
• Language: English
• Subjects: Alleles; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Brain - diagnostic imaging; Child; East Asian People; Etiology; functional connectivity; gene expression; Genes; Genome-Wide Association Study; Genomes; GWAS; Homozygotes; Humans; Hyperactivity; Magnetic Resonance Imaging - methods; Neural networks; Neural Pathways; Neuroimaging; Original; Peptide Synthases - genetics; predictive modeling; Retrospective Studies; Single-nucleotide polymorphism; Statistical analysis; sustained attention; TTLL11; Young Adult; Young adults
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/gbb.12835

Genetic studies on attention have mainly focused on children with attention‐deficit/hyperactivity disorder (ADHD), so little systematic research has been conducted on genetic correlates of attention performance and their potential brain mechanisms among healthy individuals. The current study included a genome‐wide association study (GWAS, N = 1145 healthy young adults) aimed to identify genes associated with sustained attention and an imaging genetics study (an independent sample of 483 healthy young adults) to examine any identified genes' influences on brain function. The GWAS found that TTLL11 showed genome‐wide significant associations with sustained attention, with rs13298112 as the most significant SNP and the GG homozygotes showing more impulsive but also more focused responses than the A allele carriers. A retrospective examination of previously published ADHD GWAS results confirmed an un‐reported, small but statistically significant effect of TTLL11 on ADHD. The imaging genetics study replicated this association and showed that the TTLL11 gene was associated with resting state activity and connectivity of the somatomoter network, and can be predicted by dorsal attention network connectivity. Specifically, the GG homozygotes showed lower brain activity, weaker brain network connectivity, and non‐significant brain‐attention association compared to the A allele carriers. Expression database showed that expression of this gene is enriched in the brain and that the G allele is associated with lower expression level than the A allele. These results suggest that TTLL11 may play a major role in healthy individuals' attention performance and may also contribute to the etiology of ADHD. TLL11 showed genome‐wide significant associations with sustained attention. The significant effect of TTLL11 on attention‐deficit/hyperactivity disorder (ADHD) was confirmed in two ADHD genome‐wide association study results. TTLL11 modulated the association between brain activity and sustained attention.