Epistatic interactions of genetic loci associated with age-related macular degeneration

Abstract The currently largest genome-wide association study (GWAS) for age-related macular degeneration (AMD) defines disease association with genome-wide significance for 52 independent common and rare genetic variants across 34 chromosomal loci. Overall, these loci contain over 7200 variants and...

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Autores principales:	Christina Kiel, Christoph A. Nebauer, Tobias Strunz, Simon Stelzl, Bernhard H. F. Weber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4f2b1aa556848daa51932e3f871c3ac
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spelling	oai:doaj.org-article:a4f2b1aa556848daa51932e3f871c3ac2021-12-02T16:05:55ZEpistatic interactions of genetic loci associated with age-related macular degeneration10.1038/s41598-021-92351-42045-2322https://doaj.org/article/a4f2b1aa556848daa51932e3f871c3ac2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92351-4https://doaj.org/toc/2045-2322Abstract The currently largest genome-wide association study (GWAS) for age-related macular degeneration (AMD) defines disease association with genome-wide significance for 52 independent common and rare genetic variants across 34 chromosomal loci. Overall, these loci contain over 7200 variants and are enriched for genes with functions indicating several shared cellular processes. Still, the precise mechanisms leading to AMD pathology are largely unknown. Here, we exploit the phenomenon of epistatic interaction to identify seemingly independent AMD-associated variants that reveal joint effects on gene expression. We focus on genetic variants associated with lipid metabolism, organization of extracellular structures, and innate immunity, specifically the complement cascade. Multiple combinations of independent variants were used to generate genetic risk scores allowing gene expression in liver to be compared between low and high-risk AMD. We identified genetic variant combinations correlating significantly with expression of 26 genes, of which 19 have not been associated with AMD before. This study defines novel targets and allows prioritizing further functional work into AMD pathobiology.Christina KielChristoph A. NebauerTobias StrunzSimon StelzlBernhard H. F. WeberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christina Kiel Christoph A. Nebauer Tobias Strunz Simon Stelzl Bernhard H. F. Weber Epistatic interactions of genetic loci associated with age-related macular degeneration
description	Abstract The currently largest genome-wide association study (GWAS) for age-related macular degeneration (AMD) defines disease association with genome-wide significance for 52 independent common and rare genetic variants across 34 chromosomal loci. Overall, these loci contain over 7200 variants and are enriched for genes with functions indicating several shared cellular processes. Still, the precise mechanisms leading to AMD pathology are largely unknown. Here, we exploit the phenomenon of epistatic interaction to identify seemingly independent AMD-associated variants that reveal joint effects on gene expression. We focus on genetic variants associated with lipid metabolism, organization of extracellular structures, and innate immunity, specifically the complement cascade. Multiple combinations of independent variants were used to generate genetic risk scores allowing gene expression in liver to be compared between low and high-risk AMD. We identified genetic variant combinations correlating significantly with expression of 26 genes, of which 19 have not been associated with AMD before. This study defines novel targets and allows prioritizing further functional work into AMD pathobiology.
format	article
author	Christina Kiel Christoph A. Nebauer Tobias Strunz Simon Stelzl Bernhard H. F. Weber
author_facet	Christina Kiel Christoph A. Nebauer Tobias Strunz Simon Stelzl Bernhard H. F. Weber
author_sort	Christina Kiel
title	Epistatic interactions of genetic loci associated with age-related macular degeneration
title_short	Epistatic interactions of genetic loci associated with age-related macular degeneration
title_full	Epistatic interactions of genetic loci associated with age-related macular degeneration
title_fullStr	Epistatic interactions of genetic loci associated with age-related macular degeneration
title_full_unstemmed	Epistatic interactions of genetic loci associated with age-related macular degeneration
title_sort	epistatic interactions of genetic loci associated with age-related macular degeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a4f2b1aa556848daa51932e3f871c3ac
work_keys_str_mv	AT christinakiel epistaticinteractionsofgeneticlociassociatedwithagerelatedmaculardegeneration AT christophanebauer epistaticinteractionsofgeneticlociassociatedwithagerelatedmaculardegeneration AT tobiasstrunz epistaticinteractionsofgeneticlociassociatedwithagerelatedmaculardegeneration AT simonstelzl epistaticinteractionsofgeneticlociassociatedwithagerelatedmaculardegeneration AT bernhardhfweber epistaticinteractionsofgeneticlociassociatedwithagerelatedmaculardegeneration
_version_	1718385166421852160

Epistatic interactions of genetic loci associated with age-related macular degeneration

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