Allele-specific expression reveals interactions between genetic variation and environment

David A Knowles; Joe R Davis; Hilary Edgington; Anil Raj; Marie-Julie Favé; Xiaowei Zhu; James B Potash; Myrna M Weissman; Jianxin Shi; Douglas F Levinson; Philip Awadalla; Sara Mostafavi; Stephen B Montgomery; Alexis Battle

doi:10.1038/nmeth.4298

Allele-specific expression reveals interactions between genetic variation and environment

Nat Methods. 2017 Jul;14(7):699-702. doi: 10.1038/nmeth.4298. Epub 2017 May 22.

Authors

David A Knowles^{1

2}, Joe R Davis¹, Hilary Edgington^{3

4}, Anil Raj¹, Marie-Julie Favé^{3

5}, Xiaowei Zhu⁶, James B Potash⁷, Myrna M Weissman⁸, Jianxin Shi⁹, Douglas F Levinson⁶, Philip Awadalla^{3

4

5}, Sara Mostafavi¹⁰, Stephen B Montgomery^{1

11}, Alexis Battle¹²

Affiliations

¹ Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
² Department of Radiology, Stanford University School of Medicine, Stanford, California, USA.
³ Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
⁴ University of Toronto, Toronto, Ontario, Canada.
⁵ CHU Sainte Justine, Montréal, Quebec, Canada.
⁶ Department of Psychiatry, Stanford University School of Medicine, Stanford, California, USA.
⁷ Department of Psychiatry, University of Iowa Hospitals &Clinics, Iowa City, Iowa, USA.
⁸ Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, New York, USA.
⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
¹⁰ Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
¹¹ Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
¹² Department of Computer Science, Johns Hopkins University, Baltimore, Maryland, USA.

Abstract

Identifying interactions between genetics and the environment (GxE) remains challenging. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on associations between environmental variables and allele-specific expression. Combining whole-blood RNA-seq with extensive environmental annotations collected from 922 human individuals, we identified 35 GxE interactions, compared with only four using standard GxE interaction testing. EAGLE provides new opportunities for researchers to identify GxE interactions using functional genomic data.

MeSH terms

Adult
Alleles*
Cohort Studies
Epigenesis, Genetic*
Female
Gene Expression Regulation*
Genetic Variation*
Humans
Male
Models, Genetic
Quantitative Trait Loci

Abstract

MeSH terms

Grants and funding