Genome-wide association study of working memory brain activation

Area of Science:

• Neurogenetics
• Cognitive Neuroscience
• Brain Imaging

Background:

• Working memory is crucial for cognitive function.
• Genetic factors influence brain activation patterns during cognitive tasks.
• Genome-wide association studies (GWAS) are powerful tools for identifying genetic variants associated with complex traits.

Purpose of the Study:

• To identify genetic variants associated with brain activation during the n-back working memory task using functional MRI.
• To investigate the heritability and reliability of brain activation in specific regions of interest (ROIs).
• To explore potential genetic underpinnings of working memory-related brain function and susceptibility to common brain disorders.

Main Methods:

• Functional MRI (fMRI) was used to measure brain activation (BOLD signal change) during an n-back task in 863 healthy twins and siblings.
• Regions of interest (ROIs) were defined based on heritability maps and group analyses.
• Genome-wide association analysis was performed on discovery (n=679) and replication (n=97) samples, examining over 500,000 genomic markers.

Main Results:

• Twenty ROIs demonstrated reliable and heritable working memory-related brain activation.
• No genetic variants reached stringent genome-wide significance after multiple testing correction.
• Thirty-one independent single nucleotide polymorphisms (SNPs) were associated with BOLD signal change at a discovery p<1x10⁻⁵, with two reaching p<1x10⁻⁷.
• SNPs near the BANK1 gene showed the strongest association with BOLD signal change in the left supramarginal gyrus.

Conclusions:

• The BANK1 gene region is a potential candidate for influencing brain activation during working memory tasks.
• BANK1's role in AKT signaling, part of the dopamine pathway, suggests a plausible mechanism for its involvement.
• Identified genetic variants may contribute to susceptibility to common disorders affecting brain function.