Academic Journal
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
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| Header | DbId: edsbas DbLabel: BASE An: edsbas.65E0FEF6 RelevancyScore: 920 AccessLevel: 3 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 920.2763671875 |
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| Items | – Name: Title Label: Title Group: Ti Data: Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Kanoni%2C+Stavroula%22">Kanoni, Stavroula</searchLink><br /><searchLink fieldCode="AR" term="%22Graham%2C+Sarah+E%2E%22">Graham, Sarah E.</searchLink><br /><searchLink fieldCode="AR" term="%22Locke%2C+Adam+E%2E%22">Locke, Adam E.</searchLink><br /><searchLink fieldCode="AR" term="%22Matteo%2C+F%22">Matteo, F</searchLink><br /><searchLink fieldCode="AR" term="%22McDaid%2C+AF%22">McDaid, AF</searchLink><br /><searchLink fieldCode="AR" term="%22Marques-Vidal%2C+P%22">Marques-Vidal, P</searchLink><br /><searchLink fieldCode="AR" term="%22Wielscher%2C+M%22">Wielscher, M</searchLink><br /><searchLink fieldCode="AR" term="%22Trompet%2C+S%22">Trompet, S</searchLink><br /><searchLink fieldCode="AR" term="%22Sattar%2C+N%22">Sattar, N</searchLink><br /><searchLink fieldCode="AR" term="%22Mollehave%2C+LT%22">Mollehave, LT</searchLink><br /><searchLink fieldCode="AR" term="%22Munz%2C+M%22">Munz, M</searchLink><br /><searchLink fieldCode="AR" term="%22Zeng%2C+L%22">Zeng, L</searchLink><br /><searchLink fieldCode="AR" term="%22Huang%2C+J%22">Huang, J</searchLink><br /><searchLink fieldCode="AR" term="%22Marouli%2C+Eirini%22">Marouli, Eirini</searchLink><br /><searchLink fieldCode="AR" term="%22Yang%2C+B%22">Yang, B</searchLink><br /><searchLink fieldCode="AR" term="%22Poveda%2C+A%22">Poveda, A</searchLink><br /><searchLink fieldCode="AR" term="%22Kurbasic%2C+A%22">Kurbasic, A</searchLink><br /><searchLink fieldCode="AR" term="%22Lamina%2C+C%22">Lamina, C</searchLink><br /><searchLink fieldCode="AR" term="%22Forer%2C+L%22">Forer, L</searchLink><br /><searchLink fieldCode="AR" term="%22Scholz%2C+M%22">Scholz, M</searchLink><br /><searchLink fieldCode="AR" term="%22Galesloot%2C+TE%22">Galesloot, TE</searchLink><br /><searchLink fieldCode="AR" term="%22Bradfeld%2C+JP%22">Bradfeld, JP</searchLink><br /><searchLink fieldCode="AR" term="%22Ruotsalainen%2C+SE%22">Ruotsalainen, SE</searchLink><br /><searchLink fieldCode="AR" term="%22Daw%2C+E%22">Daw, E</searchLink><br /><searchLink fieldCode="AR" term="%22Zajac%2C+Greg+J%2E+M%2E%22">Zajac, Greg J. 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D</searchLink><br /><searchLink fieldCode="AR" term="%22Correa%2C+A%22">Correa, A</searchLink><br /><searchLink fieldCode="AR" term="%22Veturi%2C+Y%22">Veturi, Y</searchLink><br /><searchLink fieldCode="AR" term="%22Wilson%2C+JG%22">Wilson, JG</searchLink><br /><searchLink fieldCode="AR" term="%22Lind%2C+L%22">Lind, L</searchLink><br /><searchLink fieldCode="AR" term="%22Heng%2C+C-K%22">Heng, C-K</searchLink><br /><searchLink fieldCode="AR" term="%22Nelson%2C+AE%22">Nelson, AE</searchLink><br /><searchLink fieldCode="AR" term="%22Golightly%2C+YM%22">Golightly, YM</searchLink><br /><searchLink fieldCode="AR" term="%22Wilson%2C+JF%22">Wilson, JF</searchLink><br /><searchLink fieldCode="AR" term="%22Penninx%2C+B%22">Penninx, B</searchLink><br /><searchLink fieldCode="AR" term="%22Kim%2C+H-L%22">Kim, H-L</searchLink><br /><searchLink fieldCode="AR" term="%22Attia%2C+John%22">Attia, John</searchLink><br /><searchLink fieldCode="AR" term="%22Scott%2C+RJ%22">Scott, RJ</searchLink><br 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DP</searchLink><br /><searchLink fieldCode="AR" term="%22Grarup%2C+N%22">Grarup, N</searchLink><br /><searchLink fieldCode="AR" term="%22Sever%2C+P%22">Sever, P</searchLink><br /><searchLink fieldCode="AR" term="%22Poulter%2C+N%22">Poulter, N</searchLink><br /><searchLink fieldCode="AR" term="%22Chuang%2C+L-M%22">Chuang, L-M</searchLink><br /><searchLink fieldCode="AR" term="%22Hunt%2C+KA%22">Hunt, KA</searchLink><br /><searchLink fieldCode="AR" term="%22Rotter%2C+J%22">Rotter, J</searchLink><br /><searchLink fieldCode="AR" term="%22Dantoft%2C+TM%22">Dantoft, TM</searchLink><br /><searchLink fieldCode="AR" term="%22Karpe%2C+F%22">Karpe, F</searchLink><br /><searchLink fieldCode="AR" term="%22Neville%2C+MJ%22">Neville, MJ</searchLink><br /><searchLink fieldCode="AR" term="%22Timpson%2C+NJ%22">Timpson, NJ</searchLink><br /><searchLink fieldCode="AR" term="%22Cheng%2C+C-Y%22">Cheng, C-Y</searchLink><br /><searchLink fieldCode="AR" term="%22Wong%2C+T-Y%22">Wong, T-Y</searchLink><br 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/><searchLink fieldCode="AR" term="%22Ramirez%2C+J%22">Ramirez, J</searchLink><br /><searchLink fieldCode="AR" term="%22Bork-Jensen%2C+J%22">Bork-Jensen, J</searchLink><br /><searchLink fieldCode="AR" term="%22Karhus%2C+LL%22">Karhus, LL</searchLink><br /><searchLink fieldCode="AR" term="%22Goel%2C+A%22">Goel, A</searchLink><br /><searchLink fieldCode="AR" term="%22Sabater-Lleal%2C+M%22">Sabater-Lleal, M</searchLink><br /><searchLink fieldCode="AR" term="%22Noordam%2C+R%22">Noordam, R</searchLink><br /><searchLink fieldCode="AR" term="%22Mauro%2C+P%22">Mauro, P</searchLink> – Name: Author Label: Contributors Group: Au Data: The University of Newcastle. College of Health, Medicine & Wellbeing, School of Medicine and Public Health – Name: Publisher Label: Publisher Information Group: PubInfo Data: BioMed Central (BMC) – Name: DatePubCY Label: Publication Year Group: Date Data: 2022 – Name: Subset Label: Collection Group: HoldingsInfo Data: NOVA: The University of Newcastle Research Online (Australia) – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22cholesterol%22">cholesterol</searchLink><br /><searchLink fieldCode="DE" term="%22lipids%22">lipids</searchLink><br /><searchLink fieldCode="DE" term="%22genetics%22">genetics</searchLink><br /><searchLink fieldCode="DE" term="%22genome-wide+association+study+%28GWAS%29%22">genome-wide association study (GWAS)</searchLink><br /><searchLink fieldCode="DE" term="%22SDG+3%22">SDG 3</searchLink><br /><searchLink fieldCode="DE" term="%22Sustainable+Development+Goals%22">Sustainable Development Goals</searchLink> – Name: Abstract Label: Description Group: Ab Data: Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk. – Name: TypeDocument Label: Document Type Group: TypDoc Data: article in journal/newspaper – Name: Language Label: Language Group: Lang Data: English – Name: NoteTitleSource Label: Relation Group: SrcInfo Data: Genome Biology Vol. 23, no. 268; http://hdl.handle.net/1959.13/1491694; uon:53055 – Name: URL Label: Availability Group: URL Data: http://hdl.handle.net/1959.13/1491694 – Name: Copyright Label: Rights Group: Cpyrght Data: © The Author(s) 2022. This 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. – Name: AN Label: Accession Number Group: ID Data: edsbas.65E0FEF6 |
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