Expressive

rs11090045 - ZC3H7B

Magnitude 4.5 · 8 studies on file

Reported associations

  • Genetic and neural bases of the neuroticism general factor. - Biological psychology (2023) · Kim Y, Saunders GRB, Giannelis A, Willoughby EA, DeYoung CG, Lee JJ · PubMed 37783279

    We applied structural equation modeling to conduct a genome-wide association study (GWAS) of the general factor measured by a neuroticism questionnaire administered to ∼380,000 participants in the UK Biobank. We categorized significant genetic variants as acting either through the neuroticism general factor, through other factors measured by the questionnaire, or through paths independent of any factor. Regardless of this categorization, however, significant variants tended to show concordant associations with all items. Bioinformatic analysis showed that the variants associated with the neuroticism general factor disproportionately lie near or within genes expressed in the brain. Enriched gene sets pointed to an underlying biological basis associated with brain development, synaptic fun

  • Leveraging Polygenic Functional Enrichment to Improve GWAS Power. - American journal of human genetics (2019) · Kichaev G, Bhatia G, Loh PR, Gazal S, Burch K, Freund MK, Schoech A, Pasaniuc B, Price AL · PubMed 30595370

    Functional genomics data has the potential to increase GWAS power by identifying SNPs that have a higher prior probability of association. Here, we introduce a method that leverages polygenic functional enrichment to incorporate coding, conserved, regulatory, and LD-related genomic annotations into association analyses. We show via simulations with real genotypes that the method, functionally informed novel discovery of risk loci (FINDOR), correctly controls the false-positive rate at null loci and attains a 9%-38% increase in the number of independent associations detected at causal loci, depending on trait polygenicity and sample size. We applied FINDOR to 27 independent complex traits and diseases from the interim UK Biobank release (average N = 130K). Averaged across traits, we attaine

  • Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways. - Nature genetics (2019) · Nagel M, Jansen PR, Stringer S, Watanabe K, de Leeuw CA, Bryois J, Savage JE, Hammerschlag AR, Skene NG, Muñoz-Manchado AB, White T, Tiemeier H, Linnarsson S, Hjerling-Leffler J, Polderman TJC, Sullivan PF, van der Sluis S, Posthuma D · PubMed 29942085

    Neuroticism is an important risk factor for psychiatric traits, including depression , anxiety , and schizophrenia . At the time of analysis, previous genome-wide association studies (GWAS) reported 16 genomic loci associated to neuroticism . Here we conducted a large GWAS meta-analysis (n = 449,484) of neuroticism and identified 136 independent genome-wide significant loci (124 new at the time of analysis), which implicate 599 genes. Functional follow-up analyses showed enrichment in several brain regions and involvement of specific cell types, including dopaminergic neuroblasts (P = 3.49 × 10 ), medium spiny neurons (P = 4.23 × 10 ), and serotonergic neurons (P = 1.37 × 10 ). Gene set analyses implicated three specific pathways: neurogenesis (P = 4.43

  • Minimal phenotyping yields genome-wide association signals of low specificity for major depression - Unknown journal (n.d.) · Unknown authors · PubMed 32231276

    ABSTRACT: Minimal phenotyping refers to the reliance on the use of a small number of self-reported items for disease case identification, increasingly used in genome-wide association studies (GWAS). Here we report differences in genetic architecture between depression defined by minimal phenotyping and strictly defined major depressive disorder (MDD): the former has a lower genotype-derived heritability that cannot be explained by inclusion of milder cases and a higher proportion of the genome contributing to this shared genetic liability with other conditions than for strictly defined MDD. GWAS based on minimal phenotyping definitions preferentially identifies loci that are not specific to MDD, and, although it generates highly predictive polygenic risk scores, the predictive power can be

  • Item-level analyses reveal genetic heterogeneity in neuroticism - Unknown journal (n.d.) · Unknown authors · PubMed 29500382

    ABSTRACT: Genome-wide association studies (GWAS) of psychological traits are generally conducted on (dichotomized) sums of items or symptoms (e.g., case-control status), and not on the individual items or symptoms themselves. We conduct large-scale GWAS on 12 neuroticism items and observe notable and replicable variation in genetic signal between items. Within samples, genetic correlations among the items range between 0.38 and 0.91 (mean rg = .63), indicating genetic heterogeneity in the full item set. Meta-analyzing the two samples, we identify 255 genome-wide significant independent genomic regions, of which 138 are item-specific. Genetic analyses and genetic correlations with 33 external traits support genetic differences between the items. Hierarchical clustering analysis identifi

  • Genome-wide association analyses identify distinct genetic architectures for early-onset and late-onset depression - Unknown journal (n.d.) · Unknown authors · PubMed 41233554

    ABSTRACT: Major depressive disorder (MDD) is a common and heterogeneous disorder of complex etiology. Studying more homogeneous groups stratified according to clinical characteristics, such as age of onset, can improve the identification of the underlying genetic causes and lead to more targeted treatment strategies. We leveraged Nordic biobanks with longitudinal health registries to investigate differences in the genetic architectures of early-onset (eoMDD; n = 46,708 cases) and late-onset (loMDD; n = 37,168 cases) MDD. We identified 12 genomic loci for eoMDD and two for loMDD. Overall, the two MDD subtypes correlated moderately (genetic correlation, rg = 0.58) and differed in their genetic correlations with related traits. These findings suggest that eoMDD and loMDD have part

  • 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

  • Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism - Unknown journal (n.d.) · Unknown authors · PubMed 29255261

    ABSTRACT: Neuroticism is a relatively stable personality trait characterised by negative emotionality (e.g., worry, guilt); twin study heritability ranges 30 to 50%, and SNP-based heritability ranges 6 to 15%. Increased neuroticism is associated with poorer mental and physical health, translating to high economic burden. Genome-wide association (GWA) studies of neuroticism have identified up to 11 genetic loci. Here we report 116 significant independent loci from a GWA of neuroticism in 329,821 UK Biobank participants; 15 of these replicated at P<.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = .82, SE=.03), major depr

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