We propose a resampling-based fast variable selection technique for detecting relevant single nucleotide polymorphisms (SNP) in a multi-marker mixed effect model. Due to computational complexity, current practice primarily involves testing the effect of one SNP at a time, commonly termed as ‘single SNP association analysis’. Joint modeling of genetic variants within a gene or pathway may have better power to detect associated genetic variants, especially the ones with weak effects. In this paper, we propose a computationally efficient model selection approach—based on the e-values framework—for single SNP detection in families while utilizing information on multiple SNPs simultaneously. To overcome computational bottleneck of traditional model selection methods, our method trains one single model, and utilizes a fast and scalable bootstrap procedure. We illustrate through numerical studies that our proposed method is more effective in detecting SNPs associated with a trait than either single-marker analysis using family data or model selection methods that ignore the familial dependency structure. Further, we perform gene-level analysis in Minnesota Center for Twin and Family Research (MCTFR) dataset using our method to detect several SNPs using this that have been implicated to be associated with alcohol consumption.
Bibliographical noteFunding Information:
This work is a part of the PhD thesis of the first author (SM). He was supported by the University of Minnesota Interdisciplinary Doctoral Fellowship program during this research. SB was supported by the NIH under grant R01-DA033958. MM was supported by NIH grants R01-AA09367, R01-DA05147 and R01-DA013240 for data collection and genotyping. SC was partially supported by the National Science Foundation (NSF) under grants 1737918, 1939916 and 1939956.
© 2023, The Author(s).
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Research Support, N.I.H., Extramural