Genetic contributions to Trail Making Test performance in UK Biobank

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 (r g 40.6), general cognitive function (r g 40.6), processing speed (r g 40.7) and memory (r g 40.3). 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.Molecular Psychiatry advance online publication, 19 September 2017; doi:10.1038/mp.2017.189 INTRODUCTIONThe 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 (particularly TMT B and B − A) to frontal lobe damage (in some, but not other studies 10 ) 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 also 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] Family-based and twin-based studies have provided evidence for a genetic contribution to individual differences in trail making, estimating the heritability for trail making part A between 0.23 and 0.38, and between 0.39 and 0.65...

Selectively Enhanced Development of Working Memory in Musically Trained Children and Adolescents

“…However, there is evidence that performance in the TMT is related primarily to processing speed and working memory ability, as well as fluid intelligence (Sánchez-Cubillo et al, 2009; Satterthwaite et al, 2013). These findings are supported by evidence of genetic correlations between trail-making performance, reasoning ability and general cognitive ability, processing speed, and memory (Hagenaars et al, 2018). Research has also found differences between the cognitive processes underlying TMT-A and B performance.…”

Structural brain imaging correlates of general intelligence in UK Biobank

“…It is often said to be an assessment of executive function. Though not considered a classical test of intelligence, Trails B performance is genetically and phenotypically strongly related to general intelligence as well as the cognitive domain of processing speed (Hagenaars, Cox, Hill, Davies, & Liewald, 2018; MacPherson et al, 2017; MacPherson, Allerhand, Cox, & Deary, 2019; Salthouse, 2011). In part B, participants were presented with the numbers 1–13, and the letters A-L arranged quasi-randomly on a computer screen.…”

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

“…Owing to positively skewed distributions, both TMT A and TMT B scores were log-transformed prior to further analyses. Further detail on these tests in UK Biobank has been published previously [ 43 ]. Processing speed was measured using the symbol digit substitution test, similar to the well-validated Symbol Digits Modalities Test [ 44 ], which was also part of the follow up testing wave.…”