Expressive

rs12273363 - BDNF - CBX3P1

Magnitude 2.2 · 8 studies on file

Reported associations

  • Genetic dissection of stool frequency implicates vitamin B1 metabolism and other actionable pathways in the modulation of gut motility. - Gut (2026) · Díaz-Muñoz C, Bozzarelli I, Lopera-Maya EA, Belbasis L, Lo Faro V, Camargo Tavares L, Heredia-Fernández F, Di Lorenzo B, Sinha T, Esteban Blanco C, Favé MJ, Awadalla P, Walters RG, Bonfiglio F, Zhernakova A, Sanna S, D'Amato M · PubMed 41558814

    Genetic studies of stool frequency (SF), an indirect proxy for gastrointestinal transit, may reveal therapeutically tractable pathways relevant to IBS and other dysmotility disorders. To identify genes and mechanisms involved in gut motility, providing a foundation for clinical translation. We performed a multiancestry genome-wide association study (GWAS) meta-analysis of SF in 268 606 European and East Asian individuals. Heritability and genetic correlations with other traits were estimated, and Mendelian randomisation was used to test causal relationships. GWAS signals were fine-mapped and functionally annotated to prioritise candidate genes and pathways. Findings implicating thiamine metabolism were followed-up with dietary interaction analyses in UK Biobank (UKB). SF heritability was

  • A scalable variational inference approach for increased mixed-model association power - Unknown journal (n.d.) · Unknown authors · PubMed 39789286

    ABSTRACT: The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71%

  • 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 Studies of over 30,000 Samples with Bone Mineral Density at Multiple Skeletal Sites and Its Clinical Relevance - Unknown journal (n.d.) · Unknown authors · PubMed 41206123

    ABSTRACT: Abstract The ultimate goal of a genome-wide association study (GWAS) is to translate its discoveries into clinical practice. To explore the clinical use of GWAS findings in the bone field, we conducted a GWAS of dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) traits at 11 skeletal sites, within over 30,000 European individuals from the UK Biobank. A total of 91 unique and independent loci were identified for 11 DXA-derived BMD traits and fractures, including 5 novel loci (harboring the genes ABCA1, CHSY1, CYP24A1, SWAP70, and PAX1) for 6 BMD traits. These loci exhibited evidence of association in both males and females, which could serve as independent replication. We demonstrated that each polygenic risk score (PRS) was independently associated with fra

  • Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis - Unknown journal (n.d.) · Unknown authors · PubMed 32203549

    ABSTRACT: Background Circulating lipoprotein lipids cause coronary heart disease (CHD). However, the precise way in which one or more lipoprotein lipid-related entities account for this relationship remains unclear. Using genetic instruments for lipoprotein lipid traits implemented through multivariable Mendelian randomisation (MR), we sought to compare their causal roles in the aetiology of CHD. Methods and findings We conducted a genome-wide association study (GWAS) of circulating non-fasted lipoprotein lipid traits in the UK Biobank (UKBB) for low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoprotein B to identify lipid-associated single nucleotide polymorphisms (SNPs). Using data from CARDIoGRAMplusC4D for CHD (consisting of 60,801 cases and 123,504 controls), we per

  • Decreased Circulating Very Small Low-Density Lipoprotein is Likely Causal for Age-Related Macular Degeneration - Unknown journal (n.d.) · Unknown authors · PubMed 39091897

    ABSTRACT: Objective Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models. However, whether particular metabolites causally affect the disease has yet to be established. Design A 3-tiered analysis of blood metabolites in the United Kingdom (UK) Biobank cohort to identify metabolites that differ in AMD patients with evidence for a putatively causal role in AMD. Participants A total of 72 376 donors from the UK Biobank cohort including participants with AMD (N = 

  • GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome - Unknown journal (n.d.) · Unknown authors · PubMed 34957435

    ABSTRACT: Summary Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10−8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndro

  • A genetic map of human metabolism across the allele frequency spectrum - Unknown journal (n.d.) · Unknown authors · PubMed 41044249

    ABSTRACT: Genetic studies of human metabolism have been limited in scale and allelic breadth. Here we provide a data-driven map of the genetic regulation of circulating small molecules and lipoprotein characteristics (249 traits) measured using proton nuclear magnetic resonance spectroscopy across the allele frequency spectrum in ~450,000 individuals. Trans-ancestral meta-analyses identify 29,824 locus-metabolite associations mapping to 753 regions with effects largely consistent between men and women and large ancestral groups represented in UK Biobank. We observe and classify extreme genetic pleiotropy, identify regulators of lipid metabolism, and assign effector genes at >100 loci through rare-to-common allelic series. We propose roles for genes less established in metabolic control (

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