Expressive

rs115740542 - H2BC4

Magnitude 2.2 · 8 studies on file

Reported associations

  • 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

  • Novel genetic loci associated with osteoarthritis in multi-ancestry analyses in the Million Veteran Program and UK Biobank. - Nature genetics (2022) · McDonald MN, Lakshman Kumar P, Srinivasasainagendra V, Nair A, Rocco AP, Wilson AC, Chiles JW, Richman JS, Pinson SA, Dennis RA, Jagadale V, Brown CJ, Pyarajan S, Tiwari HK, Bamman MM, Singh JA · PubMed 36411363

    Osteoarthritis is a common progressive joint disease. As no effective medical interventions are available, osteoarthritis often progresses to the end stage, in which only surgical options such as total joint replacement are available. A more thorough understanding of genetic influences of osteoarthritis is essential to develop targeted personalized approaches to treatment, ideally long before the end stage is reached. To date, there have been no large multiancestry genetic studies of osteoarthritis. Here, we leveraged the unique resources of 484,374 participants in the Million Veteran Program and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered osteoarthritis-associated genetic variation at 10 loci and replicated

  • Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 30664745

    ABSTRACT: Osteoarthritis is the most common musculoskeletal disease and the leading cause of disability globally. Here, we perform a genome-wide association study for osteoarthritis (77,052 cases and 378,169 controls), analysing 4 phenotypes: knee osteoarthritis, hip osteoarthritis, knee and/or hip osteoarthritis, and any osteoarthritis. We discover 64 signals, 52 of them novel, more than doubling the number of established disease loci. Six signals fine map to a single variant. We identify putative effector genes by integrating eQTL colocalization, fine-mapping, human rare disease, animal model, and osteoarthritis tissue expression data. We find enrichment for genes underlying monogenic forms of bone development diseases, and for the collagen formation and extracellular matrix organisation

  • MRI-derived brain iron, grey matter volume, and risk of dementia and Parkinson's disease: Observational and genetic analysis in the UK Biobank cohort - Unknown journal (n.d.) · Unknown authors · PubMed 38789058

    ABSTRACT: Background: Iron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload (haemochromatosis) causing HFE p.C282Y variant have increased risk of dementia and PD. Whether brain iron deposition is causal or secondary to the neurodegenerative processes in the general population is unclear. Methods: We analysed 39,533 UK Biobank participants of European genetic ancestry with brain MRI data. We studied brain iron estimated by R2* and quantitative susceptibility mapping (QSM) in 8 subcortical regions: accumbens, amygdala, caudate, hippocampus, pallidum, putamen, substantia nigra, and thalamus. We performed genome-wide associations studies (GWAS) and used Mendelian Randomization (MR) method

  • Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program - Unknown journal (n.d.) · Unknown authors · PubMed 39024449

    ABSTRACT: INTRODUCTION: Findings from genome-wide association studies (GWASs) have provided foundational knowledge of the genetic basis of disease, facilitating precision approaches for prevention and treatment. Current GWAS results are limited by underrepresentation of individuals from diverse populations, leading to concerns with generalizability regarding our knowledge of the relationships between genes, traits, and disease. The Department of Veterans Affairs (VA) Million Veteran Program (MVP), one of the largest US-based biobanks, addresses this need; 29% of MVP comprises individuals genetically similar to African (AFR), Admixed American (AMR), and East Asian (EAS) reference populations. With over 635,000 participants and more than 44.3M genotyped variants linked with detailed phenotyp

  • Trans-ethnic and ancestry-specific blood-cell genetics in 746,667 individuals from 5 global populations - Unknown journal (n.d.) · Unknown authors · PubMed 32888493

    ABSTRACT: SUMMARY Most loci identified by GWAS have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at P<5×10−9, including 71 novel loci not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional, and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value

  • GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer - Unknown journal (n.d.) · Unknown authors · PubMed 34021172

    ABSTRACT: Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to can

  • 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

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