Expressive

rs10774018 - CACNA1C

Magnitude 2.2 · 5 studies on file

Reported associations

  • Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease. - Nature medicine (2019) · Karlsson T, Rask-Andersen M, Pan G, Höglund J, Wadelius C, Ek WE, Johansson Å · PubMed 31501611

    Visceral adipose tissue (VAT)-fat stored around the internal organs-has been suggested as an independent risk factor for cardiovascular and metabolic disease , as well as all-cause, cardiovascular-specific and cancer-specific mortality . Yet, the contribution of genetics to VAT, as well as its disease-related effects, are largely unexplored due to the requirement for advanced imaging technologies to accurately measure VAT. Here, we develop sex-stratified, nonlinear prediction models (coefficient of determination = 0.76; typical 95% confidence interval (CI) = 0.74-0.78) for VAT mass using the UK Biobank cohort. We performed a genome-wide association study for predicted VAT mass and identified 102 novel visceral adiposity loci. Predicted VAT mass was associated with increased risk

  • Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling - Unknown journal (n.d.) · Unknown authors · PubMed 40759756

    ABSTRACT: Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Here we perform a multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits, which identifies 408 genomic risk loci. Our model includes a general factor of genetic overlap across all deficits, plus six new factors indexing a shared genetic signal across specific groups of deficits. We demonstrate the added clinical and etiological value of the six factors, including pr

  • Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood - Unknown journal (n.d.) · Unknown authors · PubMed 37280435

    ABSTRACT: Aims/hypothesis Determining how high BMI at different time points influences the risk of developing type 2 diabetes and affects insulin secretion and insulin sensitivity is critical. Methods By estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from those of high adulthood BMI on the risk of type 2 diabetes and insulin-related phenotypes using Mendelian randomisation. We performed two-sample MR using external studies of type 2 diabetes, and oral and intravenous measures of insulin secretion and sensitivity. Results We found tha

  • 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%

  • Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study - Unknown journal (n.d.) · Unknown authors · PubMed 32376654

    ABSTRACT: Abstract Objective To evaluate whether body size in early life has an independent effect on risk of disease in later life or whether its influence is mediated by body size in adulthood. Design Two sample univariable and multivariable mendelian randomisation. Setting The UK Biobank prospective cohort study and four large scale genome-wide association studies (GWAS) consortiums. Participants 453 169 participants enrolled in UK Biobank and a combined total of more than 700 000 people from different GWAS consortiums. Exposures Measured body mass index during adulthood (mean age 56.5) and self-reported perceived body size at age 10. Main outcome measures Coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer. Results Having a larger genetically predicted body

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