Expressive

rs10874938 - LINC02607

Magnitude 2.2 · 8 studies on file

Reported associations

  • A General Dimension of Genetic Sharing across Diverse Cognitive Traits Inferred from Molecular Data - Unknown journal (n.d.) · Unknown authors · PubMed 32895543

    ABSTRACT: It has been known since 1904 that, in humans, diverse cognitive traits are positively inter correlated. This forms the basis for the general factor of intelligence (g). Here, we directly test whether there is a partial genetic basis for individual differences in g using data from seven different cognitive tests (N = 11,263 to N = 331,679) and genome-wide autosomal single nucleotide polymorphisms. A genetic g factor accounts for an average of 58.4% (SE = 4.8%) of the genetic variance in the cognitive traits, with the proportion varying widely across traits (range: 9% to 95%). We distill genetic loci that are broadly relevant for many cognitive traits (g) from loci associated specifically with individual cognitive traits. These results contribute to elucidating the etiology of a lo

  • Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling - Unknown journal (n.d.) · Unknown authors · PubMed 40759756

    ABSTRACT: Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Here we perform a multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits, which identifies 408 genomic risk loci. Our model includes a general factor of genetic overlap across all deficits, plus six new factors indexing a shared genetic signal across specific groups of deficits. We demonstrate the added clinical and etiological value of the six factors, including pr

  • Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline - Unknown journal (n.d.) · Unknown authors · PubMed 40374629

    ABSTRACT: Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up with LD-score regression and Mendelian Randomization (MR) analyses. Focusing on global cognitive and physical function, we observed marked differences between baseline function (θ) and accelerated decline (Δ). Both outcomes showed distinct heritability levels (e.g., 31.38% versus 3.15%

  • Gene discovery and polygenic prediction from a 1.1-million-person GWAS of educational attainment - Unknown journal (n.d.) · Unknown authors · PubMed 30038396

    ABSTRACT: We conduct a large-scale genetic association analysis of educational attainment in a sample of ~1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of ~0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of

  • Genome-Wide Association Study Shows that Executive Functioning Is Influenced by GABAergic Processes and Is a Neurocognitive Genetic Correlate of Psychiatric Disorders - Unknown journal (n.d.) · Unknown authors · PubMed 36150907

    ABSTRACT: Background: Deficits in executive functions (EFs), cognitive processes that control goal-directed behaviors, are associated with psychopathology and neurological disorders. Little is known about the molecular bases of EF individual differences. Prior candidate gene studies have been underpowered in their search for dopaminergic processes involved in cognitive functioning, and existing EF genome-wide association studies (GWASs) used small sample sizes and/or focused on individual tasks that are imprecise measures of EF. Methods: We conducted a GWAS of a Common EF (cEF) factor score based on multiple tasks in the UK Biobank (N=427,037 European-descent individuals). Results: We found 129 independent genome-wide significant lead variants in 112 distinct loci and that cEF was associat

  • Large-scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets - Unknown journal (n.d.) · Unknown authors · PubMed 29186694

    ABSTRACT: Summary Here, we present a large (N=107,207) genome-wide association study (GWAS) of general cognitive ability (g), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with GCA. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker; and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most str

  • Investigating the genetic architecture of non-cognitive skills using GWAS-by-subtraction - Unknown journal (n.d.) · Unknown authors · PubMed 33414549

    ABSTRACT: Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used Genomic Structural Equation Modeling and prior genome-wide association studies (GWAS) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability.We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Non-cognitive genetics were enriched in the same brain tissues and cell types as cognitive performance but showed different associations with gray-matter brain volumes. Non-cognitive genetics were further distinguished by associations with

  • A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence - Unknown journal (n.d.) · Unknown authors · PubMed 29326435

    ABSTRACT: 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; thir

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