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Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
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A powerful and data-adaptive test for rare-variant-based gene-environment interaction analysis.

Tianzhong Yang1,2, Han Chen3,4, Hongwei Tang5

  • 1Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Statistics in Medicine
|November 22, 2018
PubMed
Summary
This summary is machine-generated.

New adaptive gene-by-environment (GxE) interaction tests, called aGE, effectively analyze rare genetic variants and environmental exposures for complex diseases. These powerful tests maintain accuracy even with numerous neutral variants, improving genetic epidemiology research.

Keywords:
data-adaptive hypothesis testinggene-environment interactionmodel misspecificationrare variant

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Area of Science:

  • Genetics
  • Epidemiology
  • Statistical genomics

Background:

  • Increasing availability of whole-exome/genome sequencing data in genetic epidemiology.
  • Emerging interest in gene-by-environment (GxE) interactions for complex diseases.
  • Challenges in testing rare-variant GxE due to neutral variants and null hypothesis estimation.

Purpose of the Study:

  • To develop powerful and data-adaptive tests for rare-variant GxE interactions.
  • To address limitations of existing methods in handling neutral variants and complex environmental effects.
  • To provide a robust statistical framework for genetic epidemiology research.

Main Methods:

  • Development of a family of adaptive GxE (aGE) tests.
  • Utilizing the adaptive powered score test framework.
  • Extensive simulations to evaluate type I error rate and power.

Main Results:

  • aGE tests control type I error rates with neutral variants and nonlinear environmental effects.
  • Demonstrated superior resilience to neutral variants compared to existing methods.
  • Successful application to Pancreatic Cancer Case-Control Consortium Exome Chip data.

Conclusions:

  • The proposed aGE tests offer a powerful and robust approach for analyzing rare-variant GxE interactions.
  • aGE tests enhance the ability to identify genetic and environmental risk factors for complex diseases.
  • An R package 'aGE' is available for public use, facilitating broader application.