scholarly journals Discovering the shared biology of cognitive traits determined by genetic overlap

2019 ◽  
Author(s):  
JPOFT Guimaraes ◽  
J Bralten ◽  
CU Greven ◽  
B Franke ◽  
E Sprooten ◽  
...  
Keyword(s):  
Functional Imaging ◽  
Fluid Intelligence ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Brain Activation ◽  
Human Cognition ◽  
Card Sorting ◽  
Human Connectome Project ◽  
Vocabulary Comprehension ◽  
Cognitive Traits

AbstractInvestigating the contribution of biology to human cognition has assumed a bottom-up causal cascade where genes influence brain systems that activate, communicate, and ultimately drive behavior. Yet few studies have directly tested whether cognitive traits with overlapping genetic underpinnings also rely on overlapping brain systems. Here, we report a step-wise exploratory analysis of genetic and functional imaging overlaps among cognitive traits. We used twin-based genetic analyses in the human connectome project (HCP) dataset (N=486), in which we quantified the heritability of measures of cognitive functions, and tested whether they were driven by common genetic factors using pairwise genetic correlations. Subsequently, we derived activation maps associated with cognitive tasks via functional imaging meta-analysis in BrainMap (N=4484), and tested whether cognitive traits that shared genetic variation also exhibited overlapping brain activation. Our genetic analysis determined that six cognitive measures (card sorting, no-go continuous performance, fluid intelligence, processing speed, reading decoding and vocabulary comprehension) were heritable (0.3<h2<0.5), and genetically correlated with at least one other heritable cognitive measure (0.2<ρg<0.35). The meta-analysis showed that two genetically-correlated traits, card sorting and fluid intelligence (ρg=0.24), also had a significant brain activation overlap (ρperm=0.29). These findings indicate that fluid intelligence and executive functioning rely on overlapping biological features, both at the neural systems level and at the molecular level. The cross-disciplinary approach we introduce provides a concrete framework for data-driven quantification of biological convergence between genetics, brain function, and behavior in health and disease.

scholarly journals Shared genetic aetiology between cognitive performance and brain activations in language and math tasks

2018 ◽  
Author(s):  
Yann Le Guen ◽  
Marie Amalric ◽  
Philippe Pinel ◽  
Christophe Pallier ◽  
Vincent Frouin
Keyword(s):  
Cognitive Ability ◽  
Cognitive Performance ◽  
Fluid Intelligence ◽  
Cognitive Task ◽  
Brain Activation ◽  
Angular Gyrus ◽  
Risk Scores ◽  
Genetic Etiology ◽  
Human Connectome Project ◽  
Shared Genetic

Cognitive performance is highly heritable. However, little is known about common genetic influences on cognitive ability and brain activation when engaged in a cognitive task. The Human Connectome Project (HCP) offers a unique opportunity to study this shared genetic etiology with an extended pedigree of 785 individuals. To investigate this common genetic origin, we took advantage of the HCP dataset, which includes both language and mathematics activation tasks. Using the HCP multimodal parcellation, we identified areals in which inter-individual functional MRI (fMRI) activation variance was significantly explained by genetics. Then, we performed bivariate genetic analyses between the neural activations and behavioral scores, corresponding to the fMRI task accuracies, fluid intelligence, working memory and language performance. We observed that several parts of the language network along the superior temporal sulcus, as well as the angular gyrus belonging to the math processing network, are significantly genetically correlated with these indicators of cognitive performance. This shared genetic etiology provides insights into the brain areas where the human-specific genetic repertoire is expressed. Studying the association of polygenic risk scores, using variants associated with human cognitive ability and brain activation, would provide an opportunity to better understand where these variants are influential.

scholarly journals EXPRESS: Trajectories of verbal fluency and executive functions in multilingual and monolingual children and adults: A cross-sectional study

2021 ◽  
pp. 174702182110267
Author(s):  
Roberto Filippi ◽  
Andrea Ceccolini ◽  
Peter Bright
Keyword(s):  
Working Memory ◽  
Executive Function ◽  
Verbal Fluency ◽  
Fluid Intelligence ◽  
Response Times ◽  
Developmental Trajectories ◽  
Cross Sectional Study ◽  
Human Cognition ◽  
Lexical Retrieval ◽  
Cross Sectional

The development of verbal fluency is associated with the maturation of executive function skills, such as the ability to inhibit irrelevant information, shift between tasks and hold information in working memory. Some evidence suggests that multilinguistic upbringing may underpin disadvantages in verbal fluency and lexical retrieval, but can also afford executive function advantages beyond the language system including possible beneficial effects in older age. This study examined the relationship between verbal fluency and executive function in 324 individuals across the lifespan by assessing the developmental trajectories of English monolingual and multilingual children aged 7 to 15 years (N=154) and adults from 18 to 80 years old (N=170). The childhood data indicated patterns of improvement in verbal fluency and executive function skills as a function of age. Multilingual and monolingual children had comparable developmental trajectories in all linguistic and non-linguistic measures used in the study with the exception of planning, for which monolingual children showed a steeper improvement over the studied age range relative to multilingual children. For adults, monolinguals and multilingual participants had comparable performance on all measures with the exception of non-verbal inhibitory control and response times on the Tower of London task: monolinguals showed a steeper decline associated with age. Exploratory factor analysis indicated that verbal fluency was associated with working memory and fluid intelligence in monolingual participants but not in multilinguals. These findings raise the possibility that early acquisition of an additional language may impact on the development of the functional architecture serving high-level human cognition.

scholarly journals Association Between Brain Activation and Functional Connectivity

2018 ◽  
Vol 29 (5) ◽  
pp. 1984-1996 ◽  
Author(s):  
Dardo Tomasi ◽  
Nora D Volkow
Keyword(s):  
Functional Connectivity ◽  
Brain Activity ◽  
Low Frequency ◽  
Brain Activation ◽  
Blood Oxygen Level Dependent ◽  
Common Source ◽  
Functional Connectivity Density ◽  
Density Mapping ◽  
Human Connectome Project ◽  
Bold Responses

Abstract The origin of the “resting-state” brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

scholarly journals Production, Reproduction and Adaptation characteristics of Boran cattle breed under changing climate: A systematic review and meta-analysis

2020 ◽  
Author(s):  
Merga Bayssa ◽  
Sintayehu Yigrem ◽  
Simret Betsa ◽  
Adugna Tolera
Keyword(s):  
Climate Change ◽  
Systematic Review ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Cattle Breed ◽  
Livestock Production ◽  
Meat Production ◽  
Zebu Cattle ◽  
Improvement Programs ◽  
Breed Improvement

AbstractIntroductionClimate change has devastating effects on livestock production and productivity, which could threaten livestock-based food security in pastoral and agro-pastoral production systems of the tropics and sub-tropics. Hence, to sustain livestock production in an environment challenged by climate change, the animals must have the ability to survive and produce under extreme conditions. Boran cattle breed is one of the hardiest Zebu cattle reared by Borana Oromo pastoralists for milk and meat production. This paper aims to compile the main production, reproduction and adaptation traits of Boran cattle based on systematic review amd meta-analysis of peer reviewed and published articles on the subject.MethodologyCombination of systematic review and meta-analysis based on PRISMA guideline was employed. Accordingly, out of 646 recorded articles identified through database searching, 64 were found to be eligible for production, reproduction and adaptation characteristics of the Boran cattle, twenty-eight articles were included in qualitative systematic review while 36 articles were used for quantitative meta-analysis.ResultBoran cattle have diversity of adaptation (morphological, physiological, biochemical, metabolic, cellular and molecular) responses to the effects of climate change induced challenges - notably high temperature and solar radiation, rangeland degradation, seasonal feed and water shortages and high incidences of tropical diseases. Meta-analysis using a random-effects model showed estimates of heritability and genetic correlations for reproduction and production traits. In addition, heritability and genetic-correlation estimates found in the present study suggest that there is high genetic variability for most traits in Boran cattle, and that genetic improvement is possible for all studied traits in this breed.ConclusionThe review revealed that Boran cattle exhibit better reproduction, production and adaption potentials as compared to other indigenous zebu cattle breeds in Ethiopia under low-land, poor pasture and water conditions. On other hand, the breed is currently challenged by adverse effects of climate change and other management factors such as high rate of genetic dilution, reduced rangeland productivity, lack of organized breed improvement programs and discriminate selection of gene pool. Thus, we recommend strategic breed improvement and genetic conservation program of Boran cattle breed in collaboration with Borana pastoralists through proper quantification of important traits and estimation of the pure Boran cattle population while controlled cross breeding strategy could be used in urban and peri-urban areas for maximum utilization of adapataion and production pottential of this breed.

scholarly journals Genome-wide association meta-analysis of childhood and adolescent internalising symptoms

2020 ◽  
Author(s):  
Eshim S Jami ◽  
Anke R Hammerschlag ◽  
Hill F Ip ◽  
Andrea G Allegrini ◽  
Beben Benyamin ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Genetic Effects ◽  
Childhood Aggression ◽  
Genome Wide Association ◽  
Childhood And Adolescence ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Genome Wide

Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INToverall) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, Neffective=132,260). Stratified analyses showed rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Gene-based analyses showed significant associations with three genes: WNT3 (p=1.13×10-06), CCL26 (p=1.88×10-06), and CENPO (p=2.54×10-06). Of these, WNT3 was previously associated with neuroticism, with which INToverall also shared a strong genetic correlation (rg=0.76). Genetic correlations were also observed with adult anxiety, depression, and the wellbeing spectrum (|rg|> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range |rg|=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Overall, childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could explain both the persistence of internalising symptoms over time, and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

scholarly journals GWAS of Depression Phenotypes in the Million Veteran Program and Meta-analysis in More than 1.2 Million Participants Yields 178 Independent Risk Loci

2020 ◽  
Author(s):  
Daniel F Levey ◽  
Murray B Stein ◽  
Frank R Wendt ◽  
Gita A Pathak ◽  
Hang Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Meta Analysis ◽  
African Ancestry ◽  
Genetic Correlations ◽  
Brain Regions ◽  
Self Report ◽  
European Ancestry ◽  
Causal Variants ◽  
Using Data ◽  
Genomic Risk

We report a large meta-analysis of depression using data from the Million Veteran Program (MVP), 23andMe Inc., UK Biobank, and FinnGen; including individuals of European ancestry (n=1,154,267; 340,591 cases) and African ancestry (n=59,600; 25,843 cases). We identified 223 and 233 independent SNPs associated with depression in European ancestry and transancestral analysis, respectively. Genetic correlations within the MVP cohort across electronic health records diagnosis, survey self-report of diagnosis, and a 2-item depression screen exceeded 0.81. Using transcriptome-wide association study (TWAS) we found significant associations for gene expression in several brain regions, including hypothalamus (NEGR1, p=3.19x10-25) and nucleus accumbens (DRD2, p=1.87x10-20). 178 genomic risk loci were fine-mapped to find likely causal variants. We identified likely pathogenicity in these variants and overlapping gene expression for 17 genes from our TWAS, including TRAF3. This study sheds light on the genetic architecture of depression and provides new insight into the interrelatedness of complex psychiatric traits.

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