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June 2020 An efficient and computationally robust statistical method for analyzing case-control mother–offspring pair genetic association studies
Hong Zhang, Bhramar Mukherjee, Victoria Arthur, Gang Hu, Hagit Hochner, Jinbo Chen
Ann. Appl. Stat. 14(2): 560-584 (June 2020). DOI: 10.1214/19-AOAS1298


Case-control mother–offspring pair design has been widely adopted for studying early-life and women’s pregnancy health. It allows assessment of pre- and perinatal environmental risk factors as well as both maternal and offspring genetic risk factors. Data arising from this design is routinely analyzed using standard prospective logistic regression. Such data has two unique features: the offspring genotypes are not correlated with maternal environmental risk factors given maternal genotypes, and offspring and maternal genotypes are related through mendelian transmission. In this work, built upon a novel regression model relating maternal genotypes to environmental risk factors, we proposed a novel retrospective likelihood method that effectively utilized the two data features to increase statistical efficiency for detecting maternal and offspring genetic effects. The inference procedure was based on a profile likelihood derived using the Lagrange multiplier method, but we replaced the multipliers with their large sample limits to enable highly efficient and computationally stable estimation. We showed that our proposed estimates of odds ratio association parameters are consistent and asymptotically normally distributed and demonstrated the finite sample performance through extensive simulation studies and application to genetic association studies of birth weight and gestational diabetes mellitus.


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Hong Zhang. Bhramar Mukherjee. Victoria Arthur. Gang Hu. Hagit Hochner. Jinbo Chen. "An efficient and computationally robust statistical method for analyzing case-control mother–offspring pair genetic association studies." Ann. Appl. Stat. 14 (2) 560 - 584, June 2020.


Received: 1 June 2019; Revised: 1 September 2019; Published: June 2020
First available in Project Euclid: 29 June 2020

zbMATH: 07239874
MathSciNet: MR4117820
Digital Object Identifier: 10.1214/19-AOAS1298

Keywords: Case-control mother–offspring pair design , genetic association , profile likelihood , retrospective likelihood , saddle point problem

Rights: Copyright © 2020 Institute of Mathematical Statistics


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Vol.14 • No. 2 • June 2020
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