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Detecting fitness epistasis in recently admixed populations with genome-wide data

BACKGROUND: Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human popula...

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Autores principales: Ni, Xumin, Zhou, Mengshi, Wang, Heming, He, Karen Y., Broeckel, Uli, Hanis, Craig, Kardia, Sharon, Redline, Susan, Cooper, Richard S., Tang, Hua, Zhu, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353720/
https://www.ncbi.nlm.nih.gov/pubmed/32652930
http://dx.doi.org/10.1186/s12864-020-06874-7
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author Ni, Xumin
Zhou, Mengshi
Wang, Heming
He, Karen Y.
Broeckel, Uli
Hanis, Craig
Kardia, Sharon
Redline, Susan
Cooper, Richard S.
Tang, Hua
Zhu, Xiaofeng
author_facet Ni, Xumin
Zhou, Mengshi
Wang, Heming
He, Karen Y.
Broeckel, Uli
Hanis, Craig
Kardia, Sharon
Redline, Susan
Cooper, Richard S.
Tang, Hua
Zhu, Xiaofeng
author_sort Ni, Xumin
collection PubMed
description BACKGROUND: Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human populations as a result of limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to the strong confounding effect observed in a recently admixed population. RESULTS: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value< 8.11 × 10(− 7)) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pairs of epistatic regions. We observed multiple pairs of co-expressed genes shared by the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in the Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. CONCLUSIONS: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to improving our understanding of adaptive evolution.
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spelling pubmed-73537202020-07-15 Detecting fitness epistasis in recently admixed populations with genome-wide data Ni, Xumin Zhou, Mengshi Wang, Heming He, Karen Y. Broeckel, Uli Hanis, Craig Kardia, Sharon Redline, Susan Cooper, Richard S. Tang, Hua Zhu, Xiaofeng BMC Genomics Research Article BACKGROUND: Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human populations as a result of limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to the strong confounding effect observed in a recently admixed population. RESULTS: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value< 8.11 × 10(− 7)) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pairs of epistatic regions. We observed multiple pairs of co-expressed genes shared by the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in the Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. CONCLUSIONS: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to improving our understanding of adaptive evolution. BioMed Central 2020-07-11 /pmc/articles/PMC7353720/ /pubmed/32652930 http://dx.doi.org/10.1186/s12864-020-06874-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Ni, Xumin
Zhou, Mengshi
Wang, Heming
He, Karen Y.
Broeckel, Uli
Hanis, Craig
Kardia, Sharon
Redline, Susan
Cooper, Richard S.
Tang, Hua
Zhu, Xiaofeng
Detecting fitness epistasis in recently admixed populations with genome-wide data
title Detecting fitness epistasis in recently admixed populations with genome-wide data
title_full Detecting fitness epistasis in recently admixed populations with genome-wide data
title_fullStr Detecting fitness epistasis in recently admixed populations with genome-wide data
title_full_unstemmed Detecting fitness epistasis in recently admixed populations with genome-wide data
title_short Detecting fitness epistasis in recently admixed populations with genome-wide data
title_sort detecting fitness epistasis in recently admixed populations with genome-wide data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353720/
https://www.ncbi.nlm.nih.gov/pubmed/32652930
http://dx.doi.org/10.1186/s12864-020-06874-7
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