rs11875397 - KC6 - NPM1P1
Magnitude 4.5 · 4 studies on file
Reported associations
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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
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Symptom-level modelling unravels the shared genetic architecture of anxiety and depression. - Nature human behaviour (2021) · Thorp JG, Campos AI, Grotzinger AD, Gerring ZF, An J, Ong JS, Wang W, Shringarpure S, Byrne EM, MacGregor S, Martin NG, Medland SE, Middeldorp CM, Derks EM · PubMed 33859377
Depression and anxiety are highly prevalent and comorbid psychiatric traits that cause considerable burden worldwide. Here we use factor analysis and genomic structural equation modelling to investigate the genetic factor structure underlying 28 items assessing depression, anxiety and neuroticism, a closely related personality trait. Symptoms of depression and anxiety loaded on two distinct, although highly genetically correlated factors, and neuroticism items were partitioned between them. We used this factor structure to conduct genome-wide association analyses on latent factors of depressive symptoms (89 independent variants, 61 genomic loci) and anxiety symptoms (102 variants, 73 loci) in the UK Biobank. Of these associated variants, 72% and 78%, respectively, replicated in an independ
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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
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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
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