Predicting cumulative risk of disease onset by redistributing weights

Stat Med. 2015 Jul 20;34(16):2427-43. doi: 10.1002/sim.6499. Epub 2015 Apr 6.

Abstract

We propose a simple approach predicting the cumulative risk of disease accommodating predictors with time-varying effects and outcomes subject to censoring. We use a nonparametric function for the coefficient of the time-varying effect and handle censoring through self-consistency equations that redistribute the probability mass of censored outcomes to the right. The computational procedure is extremely convenient and can be implemented by standard software. We prove large sample properties of the proposed estimator and evaluate its finite sample performance through simulation studies. We apply the method to estimate the cumulative risk of developing Huntington's disease (HD) from subjects with huntingtin gene mutation using a large collaborative HD study data and illustrate an inverse relationship between the cumulative risk of HD and the length of cytosine-adenine-guanine repeats in the huntingtin gene.

Keywords: Huntington's disease; proportional odds model; self-consistency equation; varying-coefficient model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Age of Onset*
  • Biostatistics
  • Computer Simulation
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Middle Aged
  • Models, Statistical
  • Monte Carlo Method
  • Nerve Tissue Proteins / genetics
  • Observational Studies as Topic / statistics & numerical data
  • Risk*
  • Statistics, Nonparametric
  • Trinucleotide Repeat Expansion

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins