Search

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

In GWAS of imaging phenotypes (e.g., by the ENIGMA and CHARGE consortia), the growing number of phenotypes considered presents a statistical challenge that other fields are not experiencing (e.g. psychiatry and the Psychiatric Genetics Consortium). However, the multivariate nature of MRI measurements may also be an advantage as many of the MRI phenotypes are correlated and multivariate methods could be considered. Here, we compared the statistical power of a multivariate GWAS versus the current univariate approach, which consists of multiple univariate analyses. To do so, we used results from twin models to estimate pertinent vectors of SNP effect sizes on brain imaging phenotypes, as well as the residual correlation matrices, necessary to estimate analytically the statistical power. We showed that for subcortical structure volumes and hippocampal subfields, a multivariate GWAS yields similar statistical power to the current univariate approach. Our analytical approach is as accurate but ~ 1000 times faster than simulations and we have released the code to facilitate the investigation of other scenarios, may they be outside the field of imaging genetics. [ABSTRACT FROM AUTHOR]

'Executive functions' (EF) is a multidimensional construct which encompasses many higher-order cognitive control operations, and is considered a potential mediator of age-associated changes in other cognitive domains. Here we examine the heritability of four measures of EF, and the genetic influences on their covariation with general cognitive abilities (GCA) from the Older Australian Twins Study. Participants included 117 pairs of monozygotic twins, 98 pairs of dizygotic twins, and 42 single twins, with a mean age of 71. Genetic modeling showed that additive genetic factors contributed to 59, 63, 29, and 31% of the variance in the four measures: working memory, verbal fluency, response inhibition and cognitive flexibility, respectively. The phenotypic associations among the four EF measures were modest, which is in line with other evidence that EF is a multi-dimensional construct. All of the covariation between the EF measures was attributable to a common genetic factor. Similarly, all of the covariation between EF and General Cognitive Ability was explained by a common genetic factor, with no significant covariance due to environmental (E) factors. The genetic correlations between the measures were moderately high, suggesting that they may have common biological underpinnings. The genetic influence in the covariation of the EF measures and GCA also suggests that some aspects of EF and GCA share the same genes or same set of genes. [ABSTRACT FROM AUTHOR]

Processing speed (PS) is one of the basic elements of cognitive functions and has been regarded as a 'common mechanism' which mediates general cognitive decline in aging. The present study of Australian twins (117 monozygotic pairs, 98 dizygotic pairs, and 42 single twins aged 65 years and over), estimated the genetic influences in five measures of PS: Digit Symbol Coding (DS), Trail Making Test A (TMTA), Stroop color naming and word reading (Stroop), Simple Reaction Time (SRT) and Complex Reaction Time (CRT); and their covariation with general cognitive ability (GCA): reasoning, problem-solving, and memory. Additive genetic factors explained 62% of the variance in DS, 42% in TMTA, 57% in Stroop, and 48% and 35% in SRT and CRT, respectively. Quantitative genetic modeling showed that all of the covariation between the five PS measures and GCA could be explained by one common genetic factor, while the covariation between the PS measures was partly explained by non-shared environmental as well as genetic influences. The genetic correlation among the PS measures was strongest for DS and TMTA, and between the PS measures and GCA was strongest for DS. These findings suggest that the different PS measures, as well as GCA were to a large extent influenced by the same set of genes and that the relationship between PS and GCA is entirely due to shared-genetic influences. [ABSTRACT FROM AUTHOR]

The region containing ROBO1 (Chromosome 3p12.3) has been implicated as a susceptibility gene for reading disorder and language deficit by translocation and linkage data. No association studies have yet been reported supporting any candidate gene. Here we report the first association of this gene with language deficits, specifically with phonological buffer deficits (a phenotype implicated in language acquisition, Specific Language Impairment and Speech Sound Disorder) and dyslexia (reading and spelling ability traits) in an unselected sample of adolescent twins and their siblings. Family-based analyses were performed on 144 tag SNPs in ROBO1, typed in 538 families with up to five offspring and tested for association with a developmental marker of language impairment (phonological buffer capacity, assessed using non word repetition).A reading and spelling ability measure-based on validated measures of lexical processing (irregular word) and grapheme-phoneme decoding (pseudo word)-and measures of short-term and working memory were also analysed. Significant association for phonological buffer capacity was observed for 21 of 144 SNPs tested, peaking at 8.70 × 10 and 9.30 × 10 for SNPs rs6803202 and rs4535189 respectively for nonword repetition, values that survive correction for multiple testing. Twenty-two SNPs showed significant associations for verbal storage (forward digit span)-a trait linked to phonological span. By contrast, just 5 SNPs reached nominal significance for working-memory, not surviving correction, and, importantly, only one SNP in the 144 tested reached nominal significance (0.04) for association with reading and spelling ability. These results provide strong support for ROBO1 as a gene involved in a core trait underpinning language acquisition, with a specific function in supporting a short-term buffer for arbitrary phonological strings. These effects of ROBO1 appear to be unrelated to brain mechanisms underpinning reading ability, at least by adolescence. While replication will be critical, the present results strongly support ROBO1 as the first gene discovered to be associated with language deficits affecting normal variation in language ability. Its functional role in neuronal migration underlying bilateral symmetry and lateralization of neuronal function further suggests a role in the evolution of human language ability. [ABSTRACT FROM AUTHOR]

Information processing speed, as measured by elementary cognitive tasks, is correlated with higher order cognitive ability so that increased speed relates to improved cognitive performance. The question of whether the genetic variation in Inspection Time (IT) and Choice Reaction Time (CRT) is associated with IQ through a unitary factor was addressed in this multivariate genetic study of IT, CRT, and IQ subtest scores. The sample included 184 MZ and 206 DZ twin pairs with a mean age of 16.2 years (range 15–18 years). They were administered a visual (π-figure) IT task, a two-choice RT task, five computerized subtests of the Multidimensional Aptitude Battery, and the digit symbol substitution subtest from the WAIS-R. The data supported a factor model comprising a general, three group (verbal ability, visuospatial ability, broad speediness), and specific genetic factor structure, a shared environmental factor influencing all tests but IT, plus unique environmental factors that were largely specific to individual measures. The general genetic factor displayed factor loadings ranging between 0.35 and 0.66 for the IQ subtests, with IT and CRT loadings of -0.47 and -0.24, respectively. Results indicate that a unitary factor is insufficient to describe the entire relationship between cognitive speed measures and all IQ subtests, with independent genetic effects explaining further covariation between processing speed (especially CRT) and Digit Symbol. [ABSTRACT FROM AUTHOR]

Corrections to the article "Genetic Influences on Four Measures of Executive Functions and Their Covariation with General Cognitive Ability: The Older Australian Twins Study" are presented.

The Author Recognition Test (ART) measures print exposure and is a unique predictor of phonological and orthographic processes in reading. In a sample of adolescent and young adult twins and siblings (216 MZ/430 DZ pairs, 307 singletons; aged 11-29 years) ART scores were moderately heritable (67%) and correlated with reading and verbal abilities, with genes largely accounting for the covariance. We also examine whether high (and low) (i.e. 1SD above the mean) represents a quantitative extreme of the normal distribution. Heritability for high ART was of similar magnitude to the full sample, but, a specific genetic factor, independent from both low ART performance and high reading ability, accounted for 53-58% of the variance. This suggests a distinct genetic etiology for high ART ability and we speculate that the specific genetic influence is on orthographical processing, a critical factor in developing word recognition skills.