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Rare high-impact disease variants: properties and identifications

Although many genome-wide association studies have been performed, the identification of disease polymorphisms remains important. It is now suspected that many rare disease variants induce the association signal of common variants in linkage disequilibrium (LD). Based on recent development of geneti...

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Autores principales: PARK, LEEYOUNG, KIM, JU HAN
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865157/
https://www.ncbi.nlm.nih.gov/pubmed/26996452
http://dx.doi.org/10.1017/S0016672316000033
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author PARK, LEEYOUNG
KIM, JU HAN
author_facet PARK, LEEYOUNG
KIM, JU HAN
author_sort PARK, LEEYOUNG
collection PubMed
description Although many genome-wide association studies have been performed, the identification of disease polymorphisms remains important. It is now suspected that many rare disease variants induce the association signal of common variants in linkage disequilibrium (LD). Based on recent development of genetic models, the current study provides explanations of the existence of rare variants with high impacts and common variants with low impacts. Disease variants are neither necessary nor sufficient due to gene–gene or gene–environment interactions. A new method was developed based on theoretical aspects to identify both rare and common disease variants by their genotypes. Common disease variants were identified with relatively small odds ratios and relatively small sample sizes, except for specific situations in which the disease variants were in strong LD with a variant with a higher frequency. Rare disease variants with small impacts were difficult to identify without increasing sample sizes; however, the method was reasonably accurate for rare disease variants with high impacts. For rare variants, dominant variants generally showed better Type II error rates than recessive variants; however, the trend was reversed for common variants. Type II error rates increased in gene regions containing more than two disease variants because the more common variant, rather than both disease variants, was usually identified. The proposed method would be useful for identifying common disease variants with small impacts and rare disease variants with large impacts when disease variants have the same effects on disease presentation.
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spelling pubmed-68651572019-11-27 Rare high-impact disease variants: properties and identifications PARK, LEEYOUNG KIM, JU HAN Genet Res (Camb) Research Papers Although many genome-wide association studies have been performed, the identification of disease polymorphisms remains important. It is now suspected that many rare disease variants induce the association signal of common variants in linkage disequilibrium (LD). Based on recent development of genetic models, the current study provides explanations of the existence of rare variants with high impacts and common variants with low impacts. Disease variants are neither necessary nor sufficient due to gene–gene or gene–environment interactions. A new method was developed based on theoretical aspects to identify both rare and common disease variants by their genotypes. Common disease variants were identified with relatively small odds ratios and relatively small sample sizes, except for specific situations in which the disease variants were in strong LD with a variant with a higher frequency. Rare disease variants with small impacts were difficult to identify without increasing sample sizes; however, the method was reasonably accurate for rare disease variants with high impacts. For rare variants, dominant variants generally showed better Type II error rates than recessive variants; however, the trend was reversed for common variants. Type II error rates increased in gene regions containing more than two disease variants because the more common variant, rather than both disease variants, was usually identified. The proposed method would be useful for identifying common disease variants with small impacts and rare disease variants with large impacts when disease variants have the same effects on disease presentation. Cambridge University Press 2016-03-21 /pmc/articles/PMC6865157/ /pubmed/26996452 http://dx.doi.org/10.1017/S0016672316000033 Text en © Cambridge University Press 2016 http://creativecommons.org/licenses/by/4.0/ This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Papers
PARK, LEEYOUNG
KIM, JU HAN
Rare high-impact disease variants: properties and identifications
title Rare high-impact disease variants: properties and identifications
title_full Rare high-impact disease variants: properties and identifications
title_fullStr Rare high-impact disease variants: properties and identifications
title_full_unstemmed Rare high-impact disease variants: properties and identifications
title_short Rare high-impact disease variants: properties and identifications
title_sort rare high-impact disease variants: properties and identifications
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865157/
https://www.ncbi.nlm.nih.gov/pubmed/26996452
http://dx.doi.org/10.1017/S0016672316000033
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