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Critical Issues in the Inclusion of Genetic and Epigenetic Information in Prevention and Intervention Trials

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Abstract

Human genetic research in the past decade has generated a wealth of data from the genome-wide association scan era, much of which is catalogued and freely available. These data will typically test the relationship between a single nucleotide variant or polymorphism (SNP) and some outcome, disease, or trait. Ongoing investigations will yield a similar wealth of data regarding epigenetic phenomena. These data will typically test the relationship between DNA methylation at a single genomic location/region and some outcome. Most of these findings will be the result of cross-sectional investigations typically using ascertained cases and controls. Consequently, most methodological consideration focuses on methods appropriate for simple case–control comparisons. It is expected that a growing number of investigators with longitudinal experimental prevention or intervention cohorts will also measure genetic and epigenetic indicators as part of their investigations, harvesting the wealth of information generated by the genome-wide association study (GWAS) era to allow for targeted hypothesis testing in the next generation of prevention and intervention trials. Herein, we discuss appropriate quality control and statistical modelling of genetic, polygenic, and epigenetic measures in longitudinal models. We specifically discuss quality control, population stratification, genotype imputation, pathway approaches, and proper modelling of an interaction between a specific genetic variant and an environment variable (GxE interaction).

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  1. Department of Psychology and Neuroscience, Baylor University, One Bear Place #97334, Waco, TX, 76798, USA

    Shawn J. Latendresse

  2. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway Ave, Baltimore, MD, 21205, USA

    Rashelle Musci & Brion S. Maher

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Correspondence to Shawn J. Latendresse or Brion S. Maher.

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This work was supported by National Institute on Drug Abuse (NIDA) Grants R01DA036525 and R01DA039408 and National Institute on Alcoholism and Alcohol Abuse Grant K01AA020333.

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Drs. Latendresse, Musci, and Maher have no potential conflicts of interest to report.

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Latendresse, S.J., Musci, R. & Maher, B.S. Critical Issues in the Inclusion of Genetic and Epigenetic Information in Prevention and Intervention Trials. Prev Sci 19, 58–67 (2018). https://doi.org/10.1007/s11121-017-0785-1

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