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1.
Nat Commun ; 11(1): 5606, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154357

RESUMO

The phenotypic correlation between human intelligence and brain volume (BV) is considerable (r ≈ 0.40), and has been shown to be due to shared genetic factors. To further examine specific genetic factors driving this correlation, we present genomic analyses of the genetic overlap between intelligence and BV using genome-wide association study (GWAS) results. First, we conduct a large BV GWAS meta-analysis (N = 47,316 individuals), followed by functional annotation and gene-mapping. We identify 18 genomic loci (14 not previously associated), implicating 343 genes (270 not previously associated) and 18 biological pathways for BV. Second, we use an existing GWAS for intelligence (N = 269,867 individuals), and estimate the genetic correlation (rg) between BV and intelligence to be 0.24. We show that the rg is partly attributable to physical overlap of GWAS hits in 5 genomic loci. We identify 92 shared genes between BV and intelligence, which are mainly involved in signaling pathways regulating cell growth. Out of these 92, we prioritize 32 that are most likely to have functional impact. These results provide information on the genetics of BV and provide biological insight into BV's shared genetic etiology with intelligence.


Assuntos
Encéfalo/anatomia & histologia , Genoma Humano/genética , Inteligência/genética , Encéfalo/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Modelos Neurológicos , Tamanho do Órgão , Locos de Características Quantitativas
2.
Am J Hum Genet ; 106(6): 885-892, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32413284

RESUMO

Leveraging high-dimensional molecular datasets can help us develop mechanistic insight into associations between genetic variants and complex traits. In this study, we integrated human proteome data derived from brain tissue to evaluate whether targeted proteins putatively mediate the effects of genetic variants on seven neurological phenotypes (Alzheimer disease, amyotrophic lateral sclerosis, depression, insomnia, intelligence, neuroticism, and schizophrenia). Applying the principles of Mendelian randomization (MR) systematically across the genome highlighted 43 effects between genetically predicted proteins derived from the dorsolateral prefrontal cortex and these outcomes. Furthermore, genetic colocalization provided evidence that the same causal variant at 12 of these loci was responsible for variation in both protein and neurological phenotype. This included genes such as DCC, which encodes the netrin-1 receptor and has an important role in the development of the nervous system (p = 4.29 × 10-11 with neuroticism), as well as SARM1, which has been previously implicated in axonal degeneration (p = 1.76 × 10-08 with amyotrophic lateral sclerosis). We additionally conducted a phenome-wide MR study for each of these 12 genes to assess potential pleiotropic effects on 700 complex traits and diseases. Our findings suggest that genes such as SNX32, which was initially associated with increased risk of Alzheimer disease, may potentially influence other complex traits in the opposite direction. In contrast, genes such as CTSH (which was also associated with Alzheimer disease) and SARM1 may make worthwhile therapeutic targets because they did not have genetically predicted effects on any of the other phenotypes after correcting for multiple testing.


Assuntos
Encéfalo/metabolismo , Variação Genética/genética , Doenças do Sistema Nervoso/genética , Fenômica , Proteoma/genética , Proteômica , Doença de Alzheimer/genética , Esclerose Amiotrófica Lateral/genética , Proteínas do Domínio Armadillo/genética , Proteínas de Transporte/genética , Catepsina H/genética , Proteínas do Citoesqueleto/genética , Depressão/genética , Estudo de Associação Genômica Ampla , Humanos , Inteligência/genética , Doenças do Sistema Nervoso/metabolismo , Neuroticismo , Proteínas Nucleares/genética , Fenótipo , Proteoma/metabolismo , Esquizofrenia/genética , Distúrbios do Início e da Manutenção do Sono/genética , Nexinas de Classificação/genética
4.
J Med Internet Res ; 22(1): e15597, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-32012058

RESUMO

BACKGROUND: The diagnosis of pigmented skin lesion is error prone and requires domain-specific expertise, which is not readily available in many parts of the world. Collective intelligence could potentially decrease the error rates of nonexperts. OBJECTIVE: The aim of this study was to evaluate the feasibility and impact of collective intelligence for the detection of skin cancer. METHODS: We created a gamified study platform on a stack of established Web technologies and presented 4216 dermatoscopic images of the most common benign and malignant pigmented skin lesions to 1245 human raters with different levels of experience. Raters were recruited via scientific meetings, mailing lists, and social media posts. Education was self-declared, and domain-specific experience was tested by screening tests. In the target test, the readers had to assign 30 dermatoscopic images to 1 of the 7 disease categories. The readers could repeat the test with different lesions at their own discretion. Collective human intelligence was achieved by sampling answers from multiple readers. The disease category with most votes was regarded as the collective vote per image. RESULTS: We collected 111,019 single ratings, with a mean of 25.2 (SD 18.5) ratings per image. As single raters, nonexperts achieved a lower mean accuracy (58.6%) than experts (68.4%; mean difference=-9.4%; 95% CI -10.74% to -8.1%; P<.001). Collectives of nonexperts achieved higher accuracies than single raters, and the improvement increased with the size of the collective. A collective of 4 nonexperts surpassed single nonexperts in accuracy by 6.3% (95% CI 6.1% to 6.6%; P<.001). The accuracy of a collective of 8 nonexperts was 9.7% higher (95% CI 9.5% to 10.29%; P<.001) than that of single nonexperts, an improvement similar to single experts (P=.73). The sensitivity for malignant images increased for nonexperts (66.3% to 77.6%) and experts (64.6% to 79.4%) for answers given faster than the intrarater mean. CONCLUSIONS: A high number of raters can be attracted by elements of gamification and Web-based marketing via mailing lists and social media. Nonexperts increase their accuracy to expert level when acting as a collective, and faster answers correspond to higher accuracy. This information could be useful in a teledermatology setting.


Assuntos
Inteligência/genética , Neoplasias Cutâneas/diagnóstico , Telemedicina/métodos , Feminino , Humanos , Internet , Masculino , Neoplasias Cutâneas/patologia
5.
Biol Psychiatry ; 87(12): 1052-1062, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061372

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown. METHODS: We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment (N = 842,499), and general intelligence (N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes. RESULTS: We identified 58 linkage disequilibrium-independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD. CONCLUSIONS: These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.


Assuntos
Sucesso Acadêmico , Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Inteligência/genética , Polimorfismo de Nucleotídeo Único
6.
Emotion ; 20(7): 1255-1265, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31259588

RESUMO

Parents want their children to be happy, educated, and successful, but are these goals related? People assume that success leads to happiness, but research on adults supports a reverse conceptualization: Happy people are more successful. Is happiness during childhood also linked to later success? Across the lifespan positive affect is linked with expanded cognitive abilities, learning, and resource building that can be adaptive and useful such that it leads to more success. Conversely, ongoing negative affect can reduce opportunities for growth and learning. Thus, happiness at any age may predict future success. Yet, no research has examined if positive and negative affect during infancy predicts childhood cognitive abilities and adult academics success. In a community sample, I hypothesized that higher infant positive affect (but not negative affect) would predict higher childhood cognitive abilities (i.e., IQ) and adult academic success (i.e., education attainment) in a 29-year study (n = 130). Positive affect, but not negative affect, during infancy (age 1.5), directly predicted higher childhood IQ (ages 6-8) and higher educational attainment (age 29), even after controlling for family socioeconomic status and infant intelligence. Childhood IQ partially explained the link between positive affect during infancy and adult educational attainment. This study advances understanding of how happiness during infancy (before formal education has begun) is linked to gold standard indicators of cognitive abilities and adult academic success. Parents, educators, and policymakers may want to place a higher value on early affective experiences when considering educational success. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Sucesso Acadêmico , Felicidade , Inteligência/genética , Adulto , Criança , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino
7.
Nat Commun ; 10(1): 5741, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31844048

RESUMO

Socioeconomic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. In a sample of 286,301 participants from UK Biobank, we identify 30 (29 previously unreported) independent-loci associated with income. Using a method to meta-analyze data from genetically-correlated traits, we identify an additional 120 income-associated loci. These loci show clear evidence of functionality, with transcriptional differences identified across multiple cortical tissues, and links to GABAergic and serotonergic neurotransmission. By combining our genome wide association study on income with data from eQTL studies and chromatin interactions, 24 genes are prioritized for follow up, 18 of which were previously associated with intelligence. We identify intelligence as one of the likely causal, partly-heritable phenotypes that might bridge the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. These results indicate that, in modern era Great Britain, genetic effects contribute towards some of the observed socioeconomic inequalities.


Assuntos
Estudo de Associação Genômica Ampla , Renda/estatística & dados numéricos , Inteligência/genética , Locos de Características Quantitativas , Classe Social , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Reino Unido
8.
Psiquiatr. biol. (Internet) ; 26(3): 105-112, sept.-dic. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-191661

RESUMO

Las personas con altas capacidades intelectuales están dotadas de un sistema cognitivo más eficiente, capaz de lograr objetivos con menos recursos. El desarrollo adecuado de este potencial es un determinante importante para la salud y el bienestar social y personal. El objetivo de este trabajo es recopilar y sintetizar los últimos hallazgos sobre los mecanismos neurobiológicos subyacentes. Los estudios de asociaciones genéticas han identificado genes y loci genéticos que generan propiedades celulares asociadas con la inteligencia. La aparición de la transcriptómica y la neurociencia celular proporcionan datos sobre el desarrollo diferencial de las células cerebrales asociadas con la alta capacidad. Los estudios de imágenes cerebrales aportan una visión macroscópica, estructural y funcional, de las áreas involucradas en la manifestación de la inteligencia. Los modelos neurocomputacionales del desarrollo cognitivo intentan explicar las trayectorias del desarrollo en función de la poligenicidad y las variaciones en el nivel de estimulación ambiental


Gifted people are endowed with a more efficient cognitive system, and capable of achieving objectives with fewer resources. The proper development of this potential is an important determinant for health and social and personal well-being. The aim of this work is to collect and analyse the latest findings on the underlying neurobiological mechanisms. Studies of genetic associations have identified genes and genetic loci that generate cellular properties associated with intelligence. The appearance of transcriptomics and cellular neuroscience provide data on the differential development of brain cells associated with giftedness. Brain imaging studies provide us with a macroscopic, structural, and functional vision of the areas involved in intelligence. The neuro-computational models of cognitive development try to explain the trajectories of development in terms of polygenicity and variations in the level of environmental stimulation


Assuntos
Humanos , Inteligência/fisiologia , Cognição/fisiologia , Cérebro/fisiologia , Inteligência/genética , Neurobiologia , Loci Gênicos/fisiologia
9.
Nat Genet ; 51(11): 1652-1659, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31676866

RESUMO

Short tandem repeats (STRs) have been implicated in a variety of complex traits in humans. However, genome-wide studies of the effects of STRs on gene expression thus far have had limited power to detect associations and provide insights into putative mechanisms. Here, we leverage whole-genome sequencing and expression data for 17 tissues from the Genotype-Tissue Expression Project to identify more than 28,000 STRs for which repeat number is associated with expression of nearby genes (eSTRs). We use fine-mapping to quantify the probability that each eSTR is causal and characterize the top 1,400 fine-mapped eSTRs. We identify hundreds of eSTRs linked with published genome-wide association study signals and implicate specific eSTRs in complex traits, including height, schizophrenia, inflammatory bowel disease and intelligence. Overall, our results support the hypothesis that eSTRs contribute to a range of human phenotypes, and our data should serve as a valuable resource for future studies of complex traits.


Assuntos
Regulação da Expressão Gênica , Genoma Humano , Estudo de Associação Genômica Ampla , Repetições de Microssatélites/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Estatura/genética , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Inflamatórias Intestinais/genética , Inteligência/genética , Esquizofrenia/genética
11.
Genes Brain Behav ; 18(8): e12602, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31385409

RESUMO

Variation in cognitive performance, which strongly predicts functional outcome in schizophrenia (SZ), has been associated with multiple immune-relevant genetic loci. These loci include complement component 4 (C4A), structural variation at which was recently associated with SZ risk and synaptic pruning during neurodevelopment and cognitive function. Here, we test whether this genetic association with cognition and SZ risk is specific to C4A, or extends more broadly to genes related to the complement system. Using a gene-set with an identified role in "complement" function (excluding C4A), we used MAGMA to test if this gene-set was enriched for genes associated with human intelligence and SZ risk, using genome-wide association summary statistics (IQ; N = 269 867, SZ; N = 105 318). We followed up this gene-set analysis with a complement gene-set polygenic score (PGS) regression analysis in an independent data set of patients with psychotic disorders and healthy participants with cognitive and genomic data (N = 1000). Enrichment analysis suggested that genes within the complement pathway were significantly enriched for genes associated with IQ, but not SZ. In a gene-based analysis of 90 genes, SERPING1 was the most enriched gene for the phenotype of IQ. In a PGS regression analysis, we found that a complement pathway PGS associated with IQ genome-wide association studies statistics also predicted variation in IQ in our independent sample. This association (observed across both patients and controls) remained significant after controlling for the relationship between C4A and cognition. These results suggest a robust association between the complement system and cognitive function, extending beyond structural variation at C4A.


Assuntos
Estudo de Associação Genômica Ampla , Inteligência/genética , Transtornos Psicóticos/genética , Adulto , Cognição , Proteína Inibidora do Complemento C1/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético
12.
Twin Res Hum Genet ; 22(3): 147-153, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31250786

RESUMO

Using newly available polygenic scores for educational attainment and cognitive ability, this paper investigates the possible presence and causes of a negative association between IQ and fertility in the Wisconsin Longitudinal Study sample, an issue that Retherford and Sewell first addressed 30 years ago. The effect of the polygenic score on the sample's reproductive characteristics was indirect: a latent cognitive ability measure, comprised of both educational attainment and IQ, wholly mediated the relationship. Age at first birth mediated the negative effect of cognitive ability on sample fertility, which had a direct (positive) effect on the number of grandchildren. Significantly greater impacts of cognitive ability on the sample's fertility characteristics were found among the female subsample. This indicates that, in this sample, having a genetic disposition toward higher cognitive ability does not directly reduce number of offspring; instead, higher cognitive ability is a risk factor for prolonging reproductive debut, which, especially for women, reduces the fertility window and, thus, the number of children and grandchildren that can be produced. By estimating the effect of the sample's reproductive characteristics on the strength of polygenic selection, it was found that the genetic variance component of IQ should be declining at a rate between -.208 (95% CI [-.020, -.383]) and -.424 (95% CI [-.041, -.766]) points per decade, depending on whether GCTA-GREML or classical behavior genetic estimates of IQ heritability are used to correct for 'missing' heritability.


Assuntos
Características da Família , Fertilidade , Inteligência/genética , Herança Multifatorial/genética , Adulto , Criança , Cognição , Feminino , Humanos , Estudos Longitudinais , Masculino
13.
J Hum Genet ; 64(8): 781-787, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165785

RESUMO

Genome-wide association studies (GWASs) have identified >20 genetic loci associated with human intelligence. However, due to correlations between the trait-associated SNPs, only a few of the loci are confirmed to have a true biological effect. In order to distinguish the SNPs that have a causal effect on human intelligence, we must eliminate the noise from the high degree of linkage disequilibrium that persists throughout the genome. In this study, we apply a novel PAINTOR fine-mapping method, which uses a Bayesian approach to determine the SNPs with the highest probability of causality. This technique incorporates the GWAS summary statistics, linkage disequilibrium structure, and functional annotations to compute the posterior probability of causality for all SNPs in the GWAS-associated regions. We found five SNPs (rs6002620, rs41352752, rs6568547, rs138592330, and rs28371699) with a high probability of causality, three of which have posterior probabilities >0.60. The SNP rs6002620 (NDUFA6), which is involved in mitochondrial function, has the highest likelihood of causality. These findings provide important insight into the genetic determinants contributing to human intelligence.


Assuntos
Mapeamento Cromossômico , Variação Genética , Inteligência/genética , Modelos Genéticos , Locos de Características Quantitativas , Característica Quantitativa Herdável , Algoritmos , Biologia Computacional/métodos , Interpretação Estatística de Dados , Bases de Dados Genéticas , Estudo de Associação Genômica Ampla , Humanos , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único
14.
Mol Psychiatry ; 24(6): 819-827, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30971729

RESUMO

Recent advances in genomics are producing powerful DNA predictors of complex traits, especially cognitive abilities. Here, we leveraged summary statistics from the most recent genome-wide association studies of intelligence and educational attainment, with highly genetically correlated traits, to build prediction models of general cognitive ability and educational achievement. To this end, we compared the performances of multi-trait genomic and polygenic scoring methods. In a representative UK sample of 7,026 children at ages 12 and 16, we show that we can now predict up to 11% of the variance in intelligence and 16% in educational achievement. We also show that predictive power increases from age 12 to age 16 and that genomic predictions do not differ for girls and boys. We found that multi-trait genomic methods were effective in boosting predictive power. Prediction accuracy varied across polygenic score approaches, however results were similar for different multi-trait and polygenic score methods. We discuss general caveats of multi-trait methods and polygenic score prediction, and conclude that polygenic scores for educational attainment and intelligence are currently the most powerful predictors in the behavioural sciences.


Assuntos
Cognição/fisiologia , Previsões/métodos , Inteligência/genética , Sucesso Acadêmico , Adolescente , Criança , Escolaridade , Feminino , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Genótipo , Humanos , Inteligência/fisiologia , Masculino , Herança Multifatorial/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
15.
Exp Neurol ; 316: 20-26, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30965038

RESUMO

Insulin resistance, broadly defined as the reduced ability of insulin to exert its biological action, has been associated with depression and cognitive dysfunction in observational studies. However, it is unclear whether these associations are causal and whether they might be underpinned by other shared factors. To address this knowledge gap, we capitalized on the stability of genetic biomarkers through the lifetime, and on their unidirectional relationship with depression and cognition. Specifically, we determined the association between quantitative measures of cognitive function and depression and genetic instruments of insulin resistance traits in two large-scale population samples, the Generation Scotland: Scottish Family Health Study (GS: SFHS; N = 19,994) and in the UK Biobank (N = 331,374). In the GS:SFHS, the polygenic risk score (PRS) for fasting insulin was associated with verbal intelligence and depression while the PRS for the homeostasis model assessment of insulin resistance was associated with verbal intelligence. Despite this overlap in genetic architecture, Mendelian randomization analyses in the GS:SFHS and in the UK Biobank samples did not yield evidence for causal associations from insulin resistance traits to either depression or cognition. These findings may be due to weak genetic instruments, limited cognitive measures and insufficient power but they may also indicate the need to identify other biological mechanisms that may mediate the relationship from insulin resistance to depression and cognition.


Assuntos
Cognição , Depressão/genética , Resistência à Insulina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Biomarcadores , Estudos de Coortes , Depressão/epidemiologia , Depressão/psicologia , Feminino , Predisposição Genética para Doença , Humanos , Inteligência/genética , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Medição de Risco , Escócia/epidemiologia , Reino Unido/epidemiologia , Adulto Jovem
16.
J Neurooncol ; 142(1): 39-48, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30607709

RESUMO

PURPOSE: Advances in the treatment of pediatric medulloblastoma have led to improved survival rates, though treatment-related toxicity leaves children with significant long-term deficits. There is significant variability in the cognitive outcome of medulloblastoma survivors, and it has been suggested that this variability may be attributable to genetic factors. The aim of this study was to explore the contributions of single nucleotide polymorphisms (SNPs) in two genes, peroxisome proliferator activated receptor (PPAR) and glutathione-S-transferase (GST), to changes in general intellectual functioning in medulloblastoma survivors. METHODS: Patients (n = 44, meanage = 6.71 years, 61.3% males) were selected on the basis of available tissue samples and neurocognitive measures. Patients received surgical tumor resection, craniospinal radiation, radiation boost to the tumor site, and multiagent chemotherapy. Genotyping analyses were completed using the Illumina Human Omni2.5 BeadChip, and 41 single nucleotide polymorphisms (SNPs) were assessed across both genes. We used a machine learning algorithm to identify polymorphisms that were significantly associated with declines in general intellectual functioning following treatment for medulloblastoma. RESULTS: We identified age at diagnosis, radiation therapy, chemotherapy, and eight SNPs associated with PPARs as predictors of general intellectual functioning. Of the eight SNPs identified, PPARα (rs6008197), PPARγ (rs13306747), and PPARδ (rs3734254) were most significantly associated with long-term changes in general intellectual functioning in medulloblastoma survivors. CONCLUSIONS: PPAR polymorphisms may predict intellectual outcome changes in children treated for medulloblastoma. Importantly, emerging evidence suggests that PPAR agonists may provide an opportunity to minimize the effects of treatment-related cognitive sequelae in these children.


Assuntos
Sobreviventes de Câncer , Neoplasias Cerebelares/genética , Glutationa Transferase/genética , Inteligência/genética , Meduloblastoma/genética , Receptores Ativados por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Meduloblastoma/patologia , Meduloblastoma/psicologia
17.
Genes Brain Behav ; 18(4): e12530, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30379395

RESUMO

Processing speed is a psychological construct that refers to the speed with which an individual can perform any cognitive operation. Processing speed correlates strongly with general cognitive ability, declines sharply with age and is impaired across a number of neurological and psychiatric disorders. Thus, identifying genes that influence processing speed will likely improve understanding of the genetics of intelligence, biological aging and the etiologies of numerous disorders. Previous genetics studies of processing speed have relied on simple phenotypes (eg, mean reaction time) derived from single tasks. This strategy assumes, erroneously, that processing speed is a unitary construct. In the present study, we aimed to characterize the genetic architecture of processing speed by using a multidimensional model applied to a battery of cognitive tasks. Linkage and QTL-specific association analyses were performed on the factors from this model. The randomly ascertained sample comprised 1291 Mexican-American individuals from extended pedigrees. We found that performance on all three distinct processing-speed factors (Psychomotor Speed; Sequencing and Shifting and Verbal Fluency) were moderately and significantly heritable. We identified a genome-wide significant quantitative trait locus (QTL) on chromosome 3q23 for Psychomotor Speed (LOD = 4.83). Within this locus, we identified a plausible and interesting candidate gene for Psychomotor Speed (Z = 2.90, P = 1.86 × 10-03 ).


Assuntos
Cromossomos Humanos Par 3/genética , Cognição , Inteligência/genética , Locos de Características Quantitativas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem
18.
J Biosoc Sci ; 51(2): 307-311, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29789024

RESUMO

Intelligence was assessed using the Standard Progressive Matrices in 316 MZ and 550 same-sex DZ twins with a mean age of 10 years in Sudan. Heritability was estimated at 0.172 and shared environmental influences at 0.596.


Assuntos
Inteligência/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Criança , Correlação de Dados , Feminino , Humanos , Masculino , Meio Social , Sudão , Adulto Jovem
19.
Mol Psychiatry ; 24(2): 182-197, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29520040

RESUMO

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N = 78,308) were meta-analyzed with a study comparing 1247 individuals with mean IQ ~170 to 8185 controls. Genes associated with intelligence implicate pyramidal neurons of the somatosensory cortex and CA1 region of the hippocampus, and midbrain embryonic GABAergic neurons. Tissue-specific analyses find the most significant enrichment for frontal cortex brain expressed genes. These results suggest specific neuronal cell types and genes may be involved in intelligence and provide new hypotheses for neuroscience experiments using model systems.


Assuntos
Inteligência/genética , Inteligência/fisiologia , Encéfalo/metabolismo , Cognição/fisiologia , Estudos de Coortes , Análise de Dados , Feminino , Lobo Frontal/metabolismo , Expressão Gênica/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Células Piramidais/fisiologia , Lobo Temporal/metabolismo
20.
Mol Psychiatry ; 24(2): 169-181, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29326435

RESUMO

Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. Education is strongly genetically correlated with intelligence (rg = 0.70). We used these findings as foundations for our use of a novel approach-multi-trait analysis of genome-wide association studies (MTAG; Turley et al. 2017)-to combine two large genome-wide association studies (GWASs) of education and intelligence, increasing statistical power and resulting in the largest GWAS of intelligence yet reported. Our study had four goals: first, to facilitate the discovery of new genetic loci associated with intelligence; second, to add to our understanding of the biology of intelligence differences; third, to examine whether combining genetically correlated traits in this way produces results consistent with the primary phenotype of intelligence; and, finally, to test how well this new meta-analytic data sample on intelligence predicts phenotypic intelligence in an independent sample. By combining datasets using MTAG, our functional sample size increased from 199,242 participants to 248,482. We found 187 independent loci associated with intelligence, implicating 538 genes, using both SNP-based and gene-based GWAS. We found evidence that neurogenesis and myelination-as well as genes expressed in the synapse, and those involved in the regulation of the nervous system-may explain some of the biological differences in intelligence. The results of our combined analysis demonstrated the same pattern of genetic correlations as those from previous GWASs of intelligence, providing support for the meta-analysis of these genetically-related phenotypes.


Assuntos
Inteligência/genética , Neurogênese/genética , Cognição/fisiologia , Análise de Dados , Feminino , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Herança Multifatorial/genética , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/fisiologia , Neurogênese/fisiologia , Polimorfismo de Nucleotídeo Único/genética
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