RT Journal Article
SR Electronic
T1 A Sparse Additive Model for High-Dimensional Interactions with an Exposure Variable
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 445304
DO 10.1101/445304
A1 Sahir R Bhatnagar
A1 Tianyuan Lu
A1 Amanda Lovato
A1 David L Olds
A1 Michael S Kobor
A1 Michael J Meaney
A1 Kieran O’Donnell
A1 Yi Yang
A1 Celia MT Greenwood
YR 2021
UL http://biorxiv.org/content/early/2021/11/30/445304.abstract
AB A conceptual paradigm for onset of a new disease is often considered to be the result of changes in entire biological networks whose states are affected by a complex interaction of genetic and environmental factors. However, when modelling a relevant phenotype as a function of high dimensional measurements, power to estimate interactions is low, the number of possible interactions could be enormous and their effects may be non-linear. In this work, we introduce a method called sail for detecting non-linear interactions with a key environmental or exposure variable in high-dimensional settings which respects the strong or weak heredity constraints. We prove that asymptotically, our method possesses the oracle property, i.e., it performs as well as if the true model were known in advance. We develop a computationally efficient fitting algorithm with automatic tuning parameter selection, which scales to high-dimensional datasets. Through an extensive simulation study, we show that sail outperforms existing penalized regression methods in terms of prediction accuracy and support recovery when there are non-linear interactions with an exposure variable. We apply sail to detect non-linear interactions between genes and a prenatal psychosocial intervention program on cognitive performance in children at 4 years of age. Results show that individuals who are genetically predisposed to lower educational attainment are those who stand to benefit the most from the intervention. Our algorithms are implemented in an R package available on CRAN (https://cran.r-project.org/package=sail).Competing Interest StatementThe authors have declared no competing interest.