The genetic correlation between educational attainment, intracranial volume and IQ is due to recent polygenic selection on general cognitive ability

2014 ◽  
Author(s):  
Davide Piffer ◽  
Emil O. W. Kirkegaard
Keyword(s):  
Educational Attainment ◽  
Cognitive Ability ◽  
Genetic Correlation ◽  
Intracranial Volume ◽  
General Cognitive Ability ◽  
Polygenic Selection

scholarly journals Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways

2019 ◽  
Author(s):  
Max Lam ◽  
W. David Hill ◽  
Joey W. Trampush ◽  
Jin Yu ◽  
Emma Knowles ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Cognitive Ability ◽  
Genetic Correlation ◽  
Allelic Variation ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Biological Mechanisms ◽  
Genetic Level ◽  
Higher Educational Attainment ◽  
Synaptic Pruning

AbstractLiability to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published GWAS in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“Concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants demonstrating the counterintuitive (“Discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education and/or schizophrenia at p<5×10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs, and many of these have been validated by larger, more recent single-phenotype GWAS. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms: early neurodevelopmental pathways that characterize concordant allelic variation, and adulthood synaptic pruning pathways that were linked to the paradoxical positive genetic association between education and schizophrenia. Further, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia, but also to the broader biological dimensions that are implicated in both general health outcomes and psychiatric illness.

scholarly journals Dissecting Biological Pathways of Psychopathology using Cognitive Genomics

2021 ◽  
Author(s):  
Max Lam ◽  
Chia-Yen Chen ◽  
W. David Hill ◽  
Charley Xia ◽  
Ruoyu Tian ◽  
...  
Keyword(s):  
Early Childhood ◽  
Correlation Analysis ◽  
Cognitive Ability ◽  
Genetic Correlation ◽  
Cognitive Deficits ◽  
Cognitive Skills ◽  
Biological Pathways ◽  
General Cognitive Ability ◽  
Gene Sets ◽  
Cognitive Dimensions

Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identified collective segments of the genome, which we call "meta-loci", that showed differential pleiotropic patterns for psychopathology relative to either General Cognitive Ability (GCA) or Non-Cognitive Skills (NCS). We observed that neurodevelopmental gene sets expressed during the prenatal-early childhood predominated in GCA-relevant meta-loci, while post-natal synaptic gene sets were more involved in NCS-relevant meta-loci. Notably, we found that GABA-ergic, cholinergic, and glutamatergic genes drove pleiotropic relationships within dissociable NCS meta-loci.

scholarly journals Does smoking cause lower educational attainment and general cognitive ability? Triangulation of causal evidence using multiple study designs

2020 ◽  
pp. 1-9
Author(s):  
Suzanne H. Gage ◽  
Hannah M. Sallis ◽  
Glenda Lassi ◽  
Robyn E. Wootton ◽  
Claire Mokrysz ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Cognitive Ability ◽  
Fluid Intelligence ◽  
Causal Effect ◽  
Smoking Initiation ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
General Cognitive Ability ◽  
Inverse Variance ◽  
Lower Educational Attainment

Abstract Background Observational studies have found associations between smoking and both poorer cognitive ability and lower educational attainment; however, evaluating causality is challenging. We used two complementary methods to explore this. Methods We conducted observational analyses of up to 12 004 participants in a cohort study (Study One) and Mendelian randomisation (MR) analyses using summary and cohort data (Study Two). Outcome measures were cognitive ability at age 15 and educational attainment at age 16 (Study One), and educational attainment and fluid intelligence (Study Two). Results Study One: heaviness of smoking at age 15 was associated with lower cognitive ability at age 15 and lower educational attainment at age 16. Adjustment for potential confounders partially attenuated findings (e.g. fully adjusted cognitive ability β −0.736, 95% CI −1.238 to −0.233, p = 0.004; fully adjusted educational attainment β −1.254, 95% CI −1.597 to −0.911, p < 0.001). Study Two: MR indicated that both smoking initiation and lifetime smoking predict lower educational attainment (e.g. smoking initiation to educational attainment inverse-variance weighted MR β −0.197, 95% CI −0.223 to −0.171, p = 1.78 × 10−49). Educational attainment results were robust to sensitivity analyses, while analyses of general cognitive ability were less so. Conclusion We find some evidence of a causal effect of smoking on lower educational attainment, but not cognitive ability. Triangulation of evidence across observational and MR methods is a strength, but the genetic variants associated with smoking initiation may be pleiotropic, suggesting caution in interpreting these results. The nature of this pleiotropy warrants further study.

scholarly journals Minimal Relationship between Local Gyrification and General Cognitive Ability in Humans

2020 ◽  
Vol 30 (6) ◽  
pp. 3439-3450
Author(s):  
Samuel R Mathias ◽  
Emma E M Knowles ◽  
Josephine Mollon ◽  
Amanda Rodrigue ◽  
Marinka M C Koenis ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Cognitive Abilities ◽  
Large Scale ◽  
Statistical Significance ◽  
Phenotypic Variance ◽  
Intracranial Volume ◽  
Cortical Surface ◽  
General Cognitive Ability ◽  
Total N ◽  
Two Samples

Abstract Previous studies suggest that gyrification is associated with superior cognitive abilities in humans, but the strength of this relationship remains unclear. Here, in two samples of related individuals (total N = 2882), we calculated an index of local gyrification (LGI) at thousands of cortical surface points using structural brain images and an index of general cognitive ability (g) using performance on cognitive tests. Replicating previous studies, we found that phenotypic and genetic LGI–g correlations were positive and statistically significant in many cortical regions. However, all LGI–g correlations in both samples were extremely weak, regardless of whether they were significant or nonsignificant. For example, the median phenotypic LGI–g correlation was 0.05 in one sample and 0.10 in the other. These correlations were even weaker after adjusting for confounding neuroanatomical variables (intracranial volume and local cortical surface area). Furthermore, when all LGIs were considered together, at least 89% of the phenotypic variance of g remained unaccounted for. We conclude that the association between LGI and g is too weak to have profound implications for our understanding of the neurobiology of intelligence. This study highlights potential issues when focusing heavily on statistical significance rather than effect sizes in large-scale observational neuroimaging studies.

scholarly journals Evidence for Recent Polygenic Selection on Educational Attainment Inferred from GWAS Hits

2016 ◽  
Author(s):  
Davide Piffer
Keyword(s):  
Educational Attainment ◽  
Cognitive Ability ◽  
Association Studies ◽  
Meta Analysis ◽  
Significant Snps ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Model Average ◽  
Polygenic Scores ◽  
Polygenic Selection

The genetic variants identified by three large genome-wide association studies (GWAS) of educational attainment were used to test a polygenic selection model. Average frequencies of alleles with positive effect (polygenic scores or PS) were compared across populations (N=26) using data from 1000 Genomes. The PS of 161 GWAS significant SNPs in a recent meta-analysis was highly correlated to population IQ (r=0.863) and to the polygenic score of four alleles independently associated with general cognitive ability. High&nbsp; correlations with PISA scores for a subsample were observed.SNP p value predicted correlation to population IQ and factors from the two previous GWAS (r= -.25). Factor analysis produced similar estimates of selection pressure for educational attainment across the three datasets. Polygenic and factor scores computed using the top 20 significant SNPs showed very high correlation to population IQ (r=0.88; 0.9). Similar findings were obtained using 52 populations from another database (ALFRED). The results together constitute a replication of preliminary findings and provide strong evidence for recent diversifying polygenic selection on educational attainment and underlying cognitive ability.

scholarly journals Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour

2018 ◽  
Author(s):  
Eleanor Sanderson ◽  
George Davey Smith ◽  
Jack Bowden ◽  
Marcus R. Munafò
Keyword(s):  
Educational Attainment ◽  
Health Outcomes ◽  
Cognitive Ability ◽  
Smoking Behaviour ◽  
Mendelian Randomisation ◽  
Individual Data ◽  
General Cognitive Ability ◽  
Uk Biobank ◽  
The Uk ◽  
Summary Data

AbstractRecent analyses have shown educational attainment to be associated with a number of health outcomes. This association may, in part, be due to an effect of educational attainment on smoking behaviour. In this study we apply a multivariable Mendelian randomisation design to determine whether the effect of educational attainment on smoking behaviour could be due to educational attainment or general cognitive ability. We use individual data from the UK Biobank study (N = 120,050) and summary data from large GWAS studies of educational attainment, cognitive ability and smoking behaviour. Our results show that more years of education are associated with a reduced likelihood of smoking which is not due to an effect of general cognitive ability on smoking behaviour. Given the considerable physical harms associated with smoking, the effect of educational attainment on smoking is likely to contribute to the health inequalities associated with differences in educational attainment.

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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