Cognitive Traits Link to Human Chromosomal Regions

Abstract

: Human cognition in normal and disease states is both environmentally and genetically mediated. Except for measures of language-specific abilities, however, few cognitive measures have been associated with specific genes or chromosomal regions. We performed genome-wide linkage analysis of five neuropsychological tests in the Collaborative Study on Genetics of Alcoholism sample. The sample included 1579 individuals (53% female, 76% White Non-Hispanic) in 217 families. There were 390 markers with mean inter-marker distance of 9.6 cM. Performance on the Digit Symbol Substitution Test, a component of the Wechsler Adult Intelligence Scale-R, showed significant linkage to 14q11.2 and suggestive linkage to 14q 24.2. This test of sustained visual attention also involves visual-motor coordination and executive functions. Performance on the WAIS-R Digit Span Test of immediate memory and mental flexibility showed suggestive linkage to 11q 25. Although the validity of these results beyond populations with a susceptibility for alcohol dependence is unclear, these results are among the first linkage results for non-language components of cognition.

A Functional Polymorphism under Positive Evolutionary Selection in ADRB2 is Associated with Human Intelligence with Opposite Effects in the Young and the Elderly

“…At the same time IQ is a highly heritable trait in humans with estimates of broad-sense heritability up to 80% (McGue et al 1993;Deary et al 2006). Genetic linkage and association studies have shown before that segregating variants influence individual differences in cognitive ability (Buyske et al 2006;Luciano et al 2006;Posthuma et al 2005). As such, human intelligence is a good ''candidate trait'' to be investigated in the context of a comparative genomic approach.…”

The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts

“…14q). [4][5][6][7] An alternative approach to gene finding is to perform genetic association tests with candidate genes that are selected based on prior knowledge of biochemical functioning. We followed the latter approach and selected a putative candidate gene that was recently shown to be involved in learning and memory, which are two major components of intelligence.…”

“…Several studies have demonstrated that the hippocampus plays a central role in learning and memory. [4][5][6][7][8] Damage to the hippocampus selectively impairs the ability to learn and remember. [8][9][10][11][12][13][14][15] The synaptosomalassociated protein of 25 kDa (SNAP-25) gene lies in an area of previous suggestive linkage to intelligence (20p12-p11.2), 3 and is highly expressed by neurons in the hippocampus.…”

Genetic contributions to Trail Making Test performance in UK Biobank

“…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 for trail making part B. [28][29][30] A recent genome-wide association study (GWAS) of trail making part A and part B in a sample of around 6000 individuals did not find any genome-wide significant hits; 31 however, GWAS of other cognitive phenotypes have demonstrated that much larger sample sizes are required to reliably identify significant genetic loci. 32,33 Trail making is thought to have genetic influences that are shared with other cognitive abilities, with a twin-based genetic correlation of 0.48 reported between trail making, measured as the ratio between trail making part A and trail making part B, and general cognitive function, and 0.52 with working memory.…”