Semiparametric analysis of complex polygenic gene-environment interactions in case-control studies

Odile Stalder, Alex Asher, Liang Liang, Raymond J. Carroll, Yanyuan Ma, Nilanjan Chatterjee

Research output: Contribution to journalArticle

Abstract

Many methods have recently been proposed for efficient analysis of case-control studies of gene-environment interactions using a retrospective likelihood framework that exploits the natural assumption of gene-environment independence in the underlying population. However, for polygenic modelling of gene-environment interactions, which is a topic of increasing scientific interest, applications of retrospective methods have been limited due to a requirement in the literature for parametric modelling of the distribution of the genetic factors.We propose a general, computationally simple, semiparametric method for analysis of case-control studies that allows exploitation of the assumption of gene-environment independence without any further parametric modelling assumptions about the marginal distributions of any of the two sets of factors. The method relies on the key observation that an underlying efficient profile likelihood depends on the distribution of genetic factors only through certain expectation terms that can be evaluated empirically.We develop asymptotic inferential theory for the estimator and evaluate its numerical performance via simulation studies. An application of the method is presented.

Original languageEnglish (US)
Pages (from-to)801-812
Number of pages12
JournalBiometrika
Volume104
Issue number4
DOIs
StatePublished - Dec 1 2017

Fingerprint

Gene-environment Interaction
Gene-Environment Interaction
Case-control Study
genotype-environment interaction
case-control studies
Case-Control Studies
Genes
Parametric Modeling
Gene
Semiparametric Methods
Profile Likelihood
Asymptotic Theory
Marginal Distribution
methodology
application methods
Exploitation
Likelihood
genes
Simulation Study
Estimator

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Mathematics(all)
  • Agricultural and Biological Sciences (miscellaneous)
  • Agricultural and Biological Sciences(all)
  • Statistics, Probability and Uncertainty
  • Applied Mathematics

Cite this

Stalder, Odile ; Asher, Alex ; Liang, Liang ; Carroll, Raymond J. ; Ma, Yanyuan ; Chatterjee, Nilanjan. / Semiparametric analysis of complex polygenic gene-environment interactions in case-control studies. In: Biometrika. 2017 ; Vol. 104, No. 4. pp. 801-812.
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Stalder, O, Asher, A, Liang, L, Carroll, RJ, Ma, Y & Chatterjee, N 2017, 'Semiparametric analysis of complex polygenic gene-environment interactions in case-control studies', Biometrika, vol. 104, no. 4, pp. 801-812. https://doi.org/10.1093/biomet/asx045

Semiparametric analysis of complex polygenic gene-environment interactions in case-control studies. / Stalder, Odile; Asher, Alex; Liang, Liang; Carroll, Raymond J.; Ma, Yanyuan; Chatterjee, Nilanjan.

In: Biometrika, Vol. 104, No. 4, 01.12.2017, p. 801-812.

Research output: Contribution to journalArticle

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