Common genetic variation and performance on standardized cognitive tests

Abstract

One surprising feature of the recently completed waves of genome-wide association studies is the limited impact of common genetic variation in individually detectable polymorphisms on many human traits. This has been particularly pronounced for studies on psychiatric conditions, which have failed to produce clear, replicable associations for common variants. One popular explanation for these negative findings is that many of these traits may be genetically heterogeneous, leading to the idea that relevant endophenotypes may be more genetically tractable. Aspects of cognition may be the most important endophenotypes for psychiatric conditions such as schizophrenia, leading many researchers to pursue large-scale studies on the genetic contributors of cognitive performance in the normal population as a surrogate for aspects of liability to disease. Here, we perform a genomewide association study with two tests of executive function, Digit Symbol and Stroop Color-Word, in 1086 healthy volunteers and with an expanded cognitive battery in 514 of these volunteers. We show that, consistent with published studies of the psychiatric conditions themselves, no single common variant has a large effect (explaining 44-8% of the population variation) on the performance of healthy individuals on standardized cognitive tests. Given that these are important endophenotypes, our work is consistent with the idea that identifying rare genetic causes of psychiatric conditions may be more important for future research than identifying genetically homogenous endophenotypes.

Whole genome association scan for genetic polymorphisms influencing information processing speed

“…Like our study, a previous genome-wide association study of digit symbol and symbol search did not uncover any genome-wide significant associations (Cirulli et al, 2010). This study was less powered than ours with a sample size of 1086 and 414 for the respective measures; none of their 100 top SNPs for each analysis overlapped with our top 100.…”

“…It is interesting to note that for symbol search, which was only measured in the LBC1936, there were associations with variables that were unmeasured in this cohort (i.e., 2-choice and 8-choice RT) suggesting that not all the common associations can be attributed to correlated type 1 error. The speed factor was most frequently nominally associated with the top hits from other variables and these were not restricted to the measures of which it was composed, suggesting that it was tapping reliable variance related to general speed processes.Like our study, a previous genome-wide association study of digit symbol and symbol search did not uncover any genome-wide significant associations (Cirulli et al, 2010). This study was less powered than ours with a sample size of 1086 and 414 for the respective measures; none of their 100 top SNPs for each analysis overlapped with our top 100.…”

Genetic Influences on Four Measures of Executive Functions and Their Covariation with General Cognitive Ability: The Older Australian Twins Study

“…This task imposes demands on Working Memory, and is distinct from Digit Span Forward, a more passive span of attention (Lezak et al 2004). Digits Span Backwards alone (without Digit Span Forward) was used or considered as a measure of Working Memory or executive function in the following studies: Bugaiska et al (2006), and Bunce and McCready (2005); Cirulli et al (2010), Luciano et al (2009. This measure will be referred to as WorkMem hereafter.…”

Bullying, Harassment, and Horizontal Violence in the Nursing Workforce The State of the Science

“…This is primarily due to the fact that cognitive or mental processes occur as antecedents to biobehavioral responses and effect behavior over time (Lupien, McEwen, Gunnar, & Heim, 2009). Genetics (temperament) and early experiences in growth and development effect neurological development and future cognitive performance (Cirulli et al, 2010); response antecedents may vary as a selective fi lter for different individuals based on their experiences with stress and coping (Olff, Langeland, & Gersons, 2005).…”