Open Access
September 2018 Confident inference for SNP effects on treatment efficacy
Ying Ding, Ying Grace Li, Yushi Liu, Stephen J. Ruberg, Jason C. Hsu
Ann. Appl. Stat. 12(3): 1727-1748 (September 2018). DOI: 10.1214/17-AOAS1128


Our research is for finding SNPs that are predictive of treatment efficacy, to decide which subgroup (with enhanced treatment efficacy) to target in drug development. Testing SNPs for lack of association with treatment outcome is inherently challenging, because any linkage disequilibrium between a noncausal SNP with a causal SNP, however small, makes the zero-null (no association) hypothesis technically false. Control of Type I error rate in testing such null hypotheses are therefore difficult to interpret. We propose a completely different formulation to address this problem. For each SNP, we provide simultaneous confidence intervals directed toward detecting possible dominant, recessive, or additive effects. Across the SNPs, we control the expected number of SNPs with at least one false confidence interval coverage. Since our confidence intervals are constructed based on pivotal statistics, the false coverage control is guaranteed to be exact and unaffected by the true values of test quantities (whether zero or nonzero). Our method is applicable to the therapeutic areas of Diabetes and Alzheimer’s diseases, and perhaps more, as a step toward confidently targeting a patient subgroup in a tailored drug development process.


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Ying Ding. Ying Grace Li. Yushi Liu. Stephen J. Ruberg. Jason C. Hsu. "Confident inference for SNP effects on treatment efficacy." Ann. Appl. Stat. 12 (3) 1727 - 1748, September 2018.


Received: 1 May 2016; Revised: 1 August 2017; Published: September 2018
First available in Project Euclid: 11 September 2018

zbMATH: 06979649
MathSciNet: MR3852695
Digital Object Identifier: 10.1214/17-AOAS1128

Keywords: multiple testing , simultaneous confidence intervals , SNP , tailored drug development , treatment efficacy

Rights: Copyright © 2018 Institute of Mathematical Statistics

Vol.12 • No. 3 • September 2018
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