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Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases
For more than a decade, genome-wide association studies have been making steady progress in discovering the causal gene variants that contribute to late-onset human diseases. Polygenic late-onset diseases in an aging population display a risk allele frequency decrease at older ages, caused by indivi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789773/ https://www.ncbi.nlm.nih.gov/pubmed/31336617 http://dx.doi.org/10.3390/jpm9030038 |
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author | Oliynyk, Roman Teo |
author_facet | Oliynyk, Roman Teo |
author_sort | Oliynyk, Roman Teo |
collection | PubMed |
description | For more than a decade, genome-wide association studies have been making steady progress in discovering the causal gene variants that contribute to late-onset human diseases. Polygenic late-onset diseases in an aging population display a risk allele frequency decrease at older ages, caused by individuals with higher polygenic risk scores becoming ill proportionately earlier and bringing about a change in the distribution of risk alleles between new cases and the as-yet-unaffected population. This phenomenon is most prominent for diseases characterized by high cumulative incidence and high heritability, examples of which include Alzheimer’s disease, coronary artery disease, cerebral stroke, and type 2 diabetes, while for late-onset diseases with relatively lower prevalence and heritability, exemplified by cancers, the effect is significantly lower. In this research, computer simulations have demonstrated that genome-wide association studies of late-onset polygenic diseases showing high cumulative incidence together with high initial heritability will benefit from using the youngest possible age-matched cohorts. Moreover, rather than using age-matched cohorts, study cohorts combining the youngest possible cases with the oldest possible controls may significantly improve the discovery power of genome-wide association studies. |
format | Online Article Text |
id | pubmed-6789773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67897732019-10-16 Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases Oliynyk, Roman Teo J Pers Med Article For more than a decade, genome-wide association studies have been making steady progress in discovering the causal gene variants that contribute to late-onset human diseases. Polygenic late-onset diseases in an aging population display a risk allele frequency decrease at older ages, caused by individuals with higher polygenic risk scores becoming ill proportionately earlier and bringing about a change in the distribution of risk alleles between new cases and the as-yet-unaffected population. This phenomenon is most prominent for diseases characterized by high cumulative incidence and high heritability, examples of which include Alzheimer’s disease, coronary artery disease, cerebral stroke, and type 2 diabetes, while for late-onset diseases with relatively lower prevalence and heritability, exemplified by cancers, the effect is significantly lower. In this research, computer simulations have demonstrated that genome-wide association studies of late-onset polygenic diseases showing high cumulative incidence together with high initial heritability will benefit from using the youngest possible age-matched cohorts. Moreover, rather than using age-matched cohorts, study cohorts combining the youngest possible cases with the oldest possible controls may significantly improve the discovery power of genome-wide association studies. MDPI 2019-07-22 /pmc/articles/PMC6789773/ /pubmed/31336617 http://dx.doi.org/10.3390/jpm9030038 Text en © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Oliynyk, Roman Teo Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases |
title | Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases |
title_full | Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases |
title_fullStr | Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases |
title_full_unstemmed | Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases |
title_short | Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases |
title_sort | evaluating the potential of younger cases and older controls cohorts to improve discovery power in genome-wide association studies of late-onset diseases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789773/ https://www.ncbi.nlm.nih.gov/pubmed/31336617 http://dx.doi.org/10.3390/jpm9030038 |
work_keys_str_mv | AT oliynykromanteo evaluatingthepotentialofyoungercasesandoldercontrolscohortstoimprovediscoverypoweringenomewideassociationstudiesoflateonsetdiseases |