Expressive

rs11620783 - NYNRIN

Magnitude 2.2 · 7 studies on file

Reported associations

  • A cross-population atlas of genetic associations for 220 human phenotypes. - Nature genetics (2021) · Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, Narita A, Konuma T, Yamamoto K, Akiyama M, Ishigaki K, Suzuki A, Suzuki K, Obara W, Yamaji K, Takahashi K, Asai S, Takahashi Y, Suzuki T, Shinozaki N, Yamaguchi H, Minami S, Murayama S, Yoshimori K, Nagayama S, Obata D, Higashiyama M, Masumoto A, Koretsune Y, Ito K, Terao C, Yamauchi T, Komuro I, Kadowaki T, Tamiya G, Yamamoto M, Nakamura Y, Kubo M, Murakami Y, Yamamoto K, Kamatani Y, Palotie A, Rivas MA, Daly MJ, Matsuda K, Okada Y · PubMed 34594039

    Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (n = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wid

  • Metabolomic investigation of major depressive disorder identifies a potentially causal association with polyunsaturated fatty acids - Unknown journal (n.d.) · Unknown authors · PubMed 36764567

    ABSTRACT: Background: Metabolic differences have been reported between individuals with and without Major Depressive Disorder (MDD), but their consistency and causal relevance has been unclear. Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in UK Biobank (N = 29, 757). We then applied 2-sample bidirectional Mendelian Randomisation (MR) and colocalization analysis to identify potentially causal relationships between each metabolite and MDD. Results: One hundred and ninety-one metabolites tested were significantly associated with MDD (PFDR < 0.05), which reduced to 129 after adjustment for likely confounders. Lower abundance of Omega-3 fatty acid measures and a higher Omega-6: Omega-3 ratio showed potentially causal effects on liabili

  • 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%

  • Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation - Unknown journal (n.d.) · Unknown authors · PubMed 35213538

    ABSTRACT: Large-scale molecular profiling and genotyping provide a unique opportunity to systematically compare the genetically predicted effects of therapeutic targets on the human metabolome. We firstly constructed genetic risk scores for 8 drug targets on the basis that they primarily modify low-density lipoprotein (LDL) cholesterol (HMGCR, PCKS9, and NPC1L1), high-density lipoprotein (HDL) cholesterol (CETP), or triglycerides (APOC3, ANGPTL3, ANGPTL4, and LPL). Conducting mendelian randomisation (MR) provided strong evidence of an effect of drug-based genetic scores on coronary artery disease (CAD) risk with the exception of ANGPTL3. We then systematically estimated the effects of each score on 249 metabolic traits derived using blood samples from an unprecedented sample size of up to

  • Discovery of novel ancestry specific genes for androgens and hypogonadism in Million Veteran Program Men - Unknown journal (n.d.) · Unknown authors · PubMed 40316537

    ABSTRACT: Given the various roles of testosterone in men's health, we conducted a multi-ancestral genetic analysis of total testosterone, free testosterone, SHBG, and hypogonadism in men within the Million Veteran Program (MVP). Here we identified 157 significant testosterone genetic variants, of which 8 have significant ancestry-specific associations. These variants implicate several genes, including SERPINF2, PRPF8, BAIAP2L1, SHBG, PRMT6, and PPIF, related to liver function. Genetic regulators of testosterone have cell type-specific effects in the testes, liver, and adrenal gland and are associated with disease risk. We conducted a meta-analysis amongst ancestry groups to identify 188 variants significantly associated with testosterone, of which 22 are novel associations. We constructe

  • Participation bias in the UK Biobank distorts genetic associations and downstream analyses - Unknown journal (n.d.) · Unknown authors · PubMed 37106081

    ABSTRACT: While volunteer-based studies such as the UK Biobank have become the cornerstone of genetic epidemiology, the participating individuals are rarely representative of their target population. To evaluate the impact of selective participation, here we derived UK Biobank participation probabilities on the basis of 14 variables harmonized across the UK Biobank and a representative sample. We then conducted weighted genome-wide association analyses on 19 traits. Comparing the output from weighted genome-wide association analyses (neffective = 94,643 to 102,215) with that from standard genome-wide association analyses (n = 263,464 to 283,749), we found that increasing representativeness led to changes in SNP effect sizes and identified novel SNP associations for 12 traits. While

  • 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 = 

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