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  1. Free, publicly-accessible full text available June 1, 2023
  2. Free, publicly-accessible full text available February 20, 2023
  3. Maex, Reinoud (Ed.)
    Semiparametric joint models of longitudinal and competing risk data are computationally costly, and their current implementations do not scale well to massive biobank data. This paper identifies and addresses some key computational barriers in a semiparametric joint model for longitudinal and competing risk survival data. By developing and implementing customized linear scan algorithms, we reduce the computational complexities from O n 2 or O n 3 to O n in various steps including numerical integration, risk set calculation, and standard error estimation, where n is the number of subjects. Using both simulated and real-world biobank data, we demonstrate that these linear scan algorithms can speed up the existing methods by a factor of up to hundreds of thousands when n > 1 0 4 , often reducing the runtime from days to minutes. We have developed an R package, FastJM, based on the proposed algorithms for joint modeling of longitudinal and competing risk time-to-event data and made it publicly available on the Comprehensive R Archive Network (CRAN).
    Free, publicly-accessible full text available February 8, 2023
  4. Free, publicly-accessible full text available July 13, 2023
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  8. Abstract Background Low-depth sequencing allows researchers to increase sample size at the expense of lower accuracy. To incorporate uncertainties while maintaining statistical power, we introduce to analyze population structure of low-depth sequencing data. Results The method optimizes the choice of nonlinear transformations of dosages to maximize the Ky Fan norm of the covariance matrix. The transformation incorporates the uncertainty in calling between heterozygotes and the common homozygotes for loci having a rare allele and is more linear when both variants are common. Conclusions We apply to samples from two indigenous Siberian populations and reveal hidden population structure accurately using only a single chromosome. The package is available on .
    Free, publicly-accessible full text available December 1, 2022
  9. Free, publicly-accessible full text available March 1, 2023
  10. Diabetes-related complications reflect longstanding damage to small and large vessels throughout the body. In addition to the duration of diabetes and poor glycemic control, genetic factors are important contributors to the variability in the development of vascular complications. Early heritability studies found strong familial clustering of both macrovascular and microvascular complications. However, they were limited by small sample sizes and large phenotypic heterogeneity, leading to less accurate estimates. We take advantage of two independent studies—UK Biobank and the Action to Control Cardiovascular Risk in Diabetes trial—to survey the single nucleotide polymorphism heritability for diabetes microvascular (diabetic kidney disease and diabetic retinopathy) and macrovascular (cardiovascular events) complications. Heritability for diabetic kidney disease was estimated at 29%. The heritability estimate for microalbuminuria ranged from 24 to 60% and was 41% for macroalbuminuria. Heritability estimates of diabetic retinopathy ranged from 6 to 33%, depending on the phenotype definition. More severe diabetes retinopathy possessed higher genetic contributions. We show, for the first time, that rare variants account for much of the heritability of diabetic retinopathy. This study suggests that a large portion of the genetic risk of diabetes complications is yet to be discovered and emphasizes the need for additional genetic studies of diabetesmore »complications.« less
    Free, publicly-accessible full text available February 8, 2023