rs10497655 - MIR548AE1 - ZNF804A

Magnitude 4.5 · 8 studies on file

Reported associations

• Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy. - Nature human behaviour (2023) · Hindley G, Shadrin AA, van der Meer D, Parker N, Cheng W, O'Connell KS, Bahrami S, Lin A, Karadag N, Holen B, Bjella T, Deary IJ, Davies G, Hill WD, Bressler J, Seshadri S, Fan CC, Ueland T, Djurovic S, Smeland OB, Frei O, Dale AM, Andreassen OA · PubMed 37365406

  Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association

• 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

• Novel loci and potential mechanisms of major depressive disorder, bipolar disorder, and schizophrenia. - Science China. Life sciences (2022) · Wang H, Yi Z, Shi T · PubMed 34159505

  Different psychiatric disorders share genetic relationships and pleiotropic loci to certain extent. We integrated and analyzed datasets related to major depressive disorder (MDD), bipolar disorder (BIP), and schizophrenia (SCZ) from the Psychiatric Genomics Consortium using multitrait analysis of genome-wide association analysis (MTAG). MTAG significantly increased the effective sample size from 99,773 to 119,754 for MDD, from 909,061 to 1,450,972 for BIP, and from 856,677 to 940,613 for SCZ. We discovered 7, 32, and 43 novel lead single nucleotide polymorphisms (SNPs) and 1, 6, and 3 novel causal SNPs for MDD, BIP, and SCZ, respectively, after fine-mapping. We identified rs8039305 in the FURIN gene as a novel pleiotropic locus across the three disorders. We performed marker analysis of ge

• Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways. - Nature genetics (2022) · Watanabe K, Jansen PR, Savage JE, Nandakumar P, Wang X, Hinds DA, Gelernter J, Levey DF, Polimanti R, Stein MB, Van Someren EJW, Smit AB, Posthuma D · PubMed 35835914

  Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment currently exists. Previous genome-wide association studies with up to 1.3 million subjects identified over 200 associated loci. This extreme polygenicity suggested that many more loci remain to be discovered. The current study almost doubled the sample size to 593,724 cases and 1,771,286 controls, thereby increasing statistical power, and identified 554 risk loci (including 364 novel loci). To capitalize on this large number of loci, we propose a novel strategy to prioritize genes using external biological resources and functional interactions between genes across risk loci. Of all 3,898 genes naively implicated from the risk loci, we prioritize 289 and find brain-tissue expression spec

• 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

• Multivariate genome-wide analyses of the well-being spectrum. - Nature genetics (2019) · Baselmans BML, Jansen R, Ip HF, van Dongen J, Abdellaoui A, van de Weijer MP, Bao Y, Smart M, Kumari M, Willemsen G, Hottenga JJ, Boomsma DI, de Geus EJC, Nivard MG, Bartels M · PubMed 30643256

  We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (N = 2,370,390), and found 304 significant independent signals. Our multivariate approaches resulted in a 26% increase in the number of independent signals relative to the four univariate GWAMAs and in an ~57% increase in the predictive power of polygenic risk scores. Supporting transcriptome- and methylome-wide analyses (TWAS and MWAS, respectively) uncovered an addition

• 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

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