Genome-wide association study of working memory brain activation

Abstract

In a population-based genome-wide association (GWA) study of n-back working memory task-related brain activation, we extracted the average percent BOLD signal change (2-back minus 0-back) from 46 regions-of-interest (ROIs) in functional MRI scans from 863 healthy twins and siblings. ROIs were obtained by creating spheres around group random effects analysis local maxima, and by thresholding a voxel-based heritability map of working memory brain activation at 50%. Quality control for test-retest reliability and heritability of ROI measures yielded 20 reliable (r>0.7) and heritable (h2>20%) ROIs. For GWA analysis, the cohort was divided into a discovery (n=679) and replication (n=97) sample. No variants survived the stringent multiple-testing-corrected genome-wide significance threshold (p<4.5×10−9), or were replicated (p<0.0016), but several genes were identified that are worthy of further investigation. A search of 529,379 genomic markers resulted in discovery of 31 independent single nucleotide polymorphisms (SNPs) associated with BOLD signal change at a discovery level of p<1×10−5. Two SNPs (rs7917410 and rs7672408) were associated at a significance level of p<1×10−7. Only one, most strongly affecting BOLD signal change in the left supramarginal gyrus (R2=5.5%), had multiple SNPs associated at p<1×10−5 in linkage disequilibrium with it, all located in and around the BANK1 gene. BANK1 encodes a B-cell-specific scaffold protein and has been shown to negatively regulate CD40-mediated AKT activation. AKT is part of the dopamine-signaling pathway, suggesting a mechanism for the involvement of BANK1 in the BOLD response to working memory. Variants identified here may be relevant to (the susceptibility to) common disorders affecting brain function.

Functional MRI in prenatally opioid-exposed children during a working memory-selective attention task

“…Genetic factors: Twin studies have shown high heritability for subcortical brain measures, 153,154 and brain activation as seen by fMRI has been shown to be under substantial genetic control. 155 However, specific genetic variants influencing these brain measures are largely unknown. 155,156 Our study had no measure suitable to control the potential influence of genetic vulnerabilities on volumetric or functional brain measures.…”

Genetic Architecture of Working Memory Cognitive Function of Twins

“…Another study to analyze the genetic and environmental influence on cognitive functions and concluded that the variations in working memory cognitive functions were due to genetic factors that contributed around 50 percent [16]. The genetic influence on working memory cognitive functions was 50% and the remaining 50 percent variations in working memory cognitive functions were due to environmental situations [17]. The study was conducted to examine the genetic influence on working memory-related task and concluded that the genes accounted for up to 65 percent variance in working memory cognitive abilities [18].…”

Neurocognitive Endophenotypes of Schizophrenia and Bipolar Disorder and Possible Associations with FKBP Variant rs3800373

“…Cognitive capability is a complex hereditary trait shaped by a great number of genes, all with relatively weak and variable influence on the cognitive phenotype of an individual. It is well-known that general cognitive capability is an individually variable but also a highly hereditary trait ( 27 ). In our results, both SCZ and BD patients needed more time to complete the TMT-A&B compared to the HC.…”