Abstract
The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B−part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg>0.6), general cognitive function (rg>0.6), processing speed (rg>0.7) and memory (rg>0.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed and memory (standardized β between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed.
Highlights
The Trail Making Test (TMT) is widely used in both research and clinical settings as a test of some aspects of executive function.[1,2,3] The TMT is usually given as two parts, from which three measures are derived
This study finds one genome-wide significant variant associated with TMT part B performance in UK Biobank, and provides the first single-nucleotide polymorphism (SNP)-based heritability estimates for the three widely used TMT measures
We identified high genetic correlations between trail making, verbalnumerical reasoning (VNR), general cognitive function and processing speed, and somewhat lower genetic correlations with memory
Summary
The Trail Making Test (TMT) is widely used in both research and clinical settings as a test of some aspects of executive function.[1,2,3] The TMT is usually given as two parts, from which three measures are derived. In TMT Part A (TMT A), participants are required to connect an array of numbers in ascending order, by drawing a continuous line (trail) between them as quickly and accurately as possible. TMT Part B (TMT B) requires participants to connect an array of both numbers and letters in alternating ascending order (1, A, 2, B, 3, C and so on) with the same emphasis on speed and accuracy (Supplementary Figure 1). Subtracting TMT A completion time from that of TMT B (TMT B − A) is thought to allow the relative contributions of visual search and psychomotor speed to be parsed from the more complex executive functions (such as cognitive flexibility) required to alternate between numbers and letters.[4,5,6,7,8]. TMT performance has been ascribed to a number of cognitive processes, ‘including attention, visual search and scanning, sequencing and shifting, psychomotor speed, abstraction, flexibility, ability to execute and modify a plan of action, and ability to maintain two trains of thought simultaneously’.9 It is considered a useful tool in research and clinical practice due to the sensitivity of the task ( TMT B and B − A) to frontal lobe damage (in some, but not other studies10) and dementia.[11,12,13] There are declines in both TMT A and B performance in ageing.[10,14,15,16,17,18,19,20] There is evidence for performance deficits on TMT B in mood disorders[21] and in patients with schizophrenia and their relatives[18,22,23,24,25,26,27]
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