scholarly journals The total burden of rare, non-synonymous exome genetic variants is not associated with childhood or late-life cognitive ability

2014 ◽  
Vol 281 (1781) ◽  
pp. 20140117 ◽  
Author(s):  
Riccardo E. Marioni ◽  
Lars Penke ◽  
Gail Davies ◽  
Jennifer E. Huffman ◽  
Caroline Hayward ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Cognitive Ability ◽  
Multiple Testing ◽  
Rare Variants ◽  
A Priori ◽  
Late Life ◽  
General Cognitive Ability ◽  
Birth Cohorts ◽  
Total Burden ◽  
Gain Loss

Human cognitive ability shows consistent, positive associations with fitness components across the life-course. Underlying genetic variation should therefore be depleted by selection, which is not observed. Genetic variation in general cognitive ability (intelligence) could be maintained by a mutation–selection balance, with rare variants contributing to its genetic architecture. This study examines the association between the total number of rare stop-gain/loss, splice and missense exonic variants and cognitive ability in childhood and old age in the same individuals. Exome array data were obtained in the Lothian Birth Cohorts of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at age 11 years and in late life (79 and 70 years, respectively) and was modelled against the total number of stop-gain/loss, splice, and missense exonic variants, with minor allele frequency less than or equal to 0.01, using linear regression adjusted for age and sex. In both cohorts and in both the childhood and late-life models, there were no significant associations between rare variant burden in the exome and cognitive ability that survived correction for multiple testing. Contrary to our a priori hypothesis, we observed no evidence for an association between the total number of rare exonic variants and either childhood cognitive ability or late-life cognitive ability.

scholarly journals Exome Sequencing to Detect Rare Variants Associated With General Cognitive Ability: A Pilot Study

2015 ◽  
Vol 18 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Michelle Luciano ◽  
Victoria Svinti ◽  
Archie Campbell ◽  
Riccardo E. Marioni ◽  
Caroline Hayward ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Exome Sequencing ◽  
Genetic Variants ◽  
Complex Traits ◽  
Rare Variants ◽  
Copy Number Variant ◽  
Apical Part ◽  
General Cognitive Ability ◽  
Sequencing Studies ◽  
Rare Genetic Variants

Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.

scholarly journals An investigation of Social Class Inequalities in General Cognitive Ability in Two British Birth Cohorts

2018 ◽  
Author(s):  
Roxanne Connelly ◽  
Vernon Gayle
Keyword(s):  
Social Class ◽  
Cognitive Ability ◽  
Test Scores ◽  
Large Scale ◽  
Parental Education ◽  
General Cognitive Ability ◽  
Birth Cohorts ◽  
Ability Test ◽  
British Cohort Study ◽  
Nationally Representative

The ‘Flynn effect’ describes the substantial and long-standing increase in average cognitive ability test scores, which has been observed in numerous psychological studies. Flynn makes an appeal for researchers to move beyond psychology’s standard disciplinary boundaries and to consider sociological contexts, in order to develop a more comprehensive understanding of cognitive inequalities. In this article we respond to this appeal and investigate social class inequalities in general cognitive ability test scores over time. We analyse data from the National Child Development Study (1958) and the British Cohort Study (1970). These two British birth cohorts are suitable nationally representative large-scale data resources for studying inequalities in general cognitive ability.We observe a large parental social class effect, net of parental education and gender in both cohorts. The overall finding is that large social class divisions in cognitive ability can be observed when children are still at primary school, and similar patterns are observed in each cohort. Notably, pupils with fathers at the lower end of the class structure are at a distinct disadvantage. This is a disturbing finding and it is especially important because cognitive ability is known to influence individuals later in the lifecourse.

scholarly journals Meta-Analysis of Genetic Variation in DTNBP1 and General Cognitive Ability

2010 ◽  
Vol 68 (12) ◽  
pp. 1126-1133 ◽  
Author(s):  
Jian-Ping Zhang ◽  
Katherine E. Burdick ◽  
Todd Lencz ◽  
Anil K. Malhotra
Keyword(s):  
Genetic Variation ◽  
Cognitive Ability ◽  
Meta Analysis ◽  
General Cognitive Ability

scholarly journals Genetic variation in DTNBP1 influences general cognitive ability

2006 ◽  
Vol 15 (10) ◽  
pp. 1563-1568 ◽  
Author(s):  
Katherine E. Burdick ◽  
Todd Lencz ◽  
Birgit Funke ◽  
Christine T. Finn ◽  
Philip R. Szeszko ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Cognitive Ability ◽  
General Cognitive Ability

scholarly journals Association of Genetic Variation in theMETProto-Oncogene With Schizophrenia and General Cognitive Ability

2010 ◽  
Vol 167 (4) ◽  
pp. 436-443 ◽  
Author(s):  
Katherine E. Burdick ◽  
Pamela DeRosse ◽  
John M. Kane ◽  
Todd Lencz ◽  
Anil K. Malhotra
Keyword(s):  
Genetic Variation ◽  
Cognitive Ability ◽  
General Cognitive Ability

Sex Differences in Childhood Associations between DNA Markers and General Cognitive Ability

2007 ◽  
Vol 28 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Rosalind Arden ◽  
Nicole Harlaar ◽  
Robert Plomin
Keyword(s):  
Sex Differences ◽  
Single Nucleotide Polymorphisms ◽  
Cognitive Ability ◽  
Dna Markers ◽  
Community Sample ◽  
Nucleotide Polymorphisms ◽  
General Cognitive Ability ◽  
Single Nucleotide ◽  
The Difference

Abstract. An association between intelligence at age 7 and a set of five single-nucleotide polymorphisms (SNPs) has been identified and replicated. We used this composite SNP set to investigate whether the associations differ between boys and girls for general cognitive ability at ages 2, 3, 4, 7, 9, and 10 years. In a longitudinal community sample of British twins aged 2-10 (n > 4,000 individuals), we found that the SNP set is more strongly associated with intelligence in males than in females at ages 7, 9, and 10 and the difference is significant at 10. If this finding replicates in other studies, these results will constitute the first evidence of the same autosomal genes acting differently on intelligence in the two sexes.

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