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Chunk #31 — Conclusion

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Critical Issues in the Inclusion of Genetic and Epigenetic Information in Prevention and Intervention Trials.
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Inclusion of genetic and epigenetic measures in longitudinal prevention studies will allow for the elucidation of the mechanism(s) by which preventive measures operate, including the detection of biological moderators and/or mediators of effectiveness. Multiple steps must be taken to ensure valid results. Appropriate quality control steps, at the SNP and individual level, must be taken to avoid inclusion of problematic genetic markers and contaminated or swapped individual samples. Careful imputation of markers using a valid reference panel will allow for the testing of nearly all genomic variation, while accounting for the uncertainty inherent to imputation. Proper approaches to accounting for genetic ancestry avoids spurious association due to population stratification. Ancestry principal components can be used as covariates in subsequent models testing genotype-phenotype relationships to prevent false positive results due to stratification. Polygenic scoring is a powerful approach to capturing composite genetic risk and may be useful for examining the impact of prevention or intervention efforts across the biological risk spectrum. Inclusion of polygenic risk as the lone genetic predictor, or in addition to a single SNP, in association testing is