000123987 001__ 123987
000123987 005__ 20240319081028.0
000123987 0247_ $$2doi$$a10.1186/s13059-022-02837-1
000123987 0248_ $$2sideral$$a132581
000123987 037__ $$aART-2022-132581
000123987 041__ $$aeng
000123987 100__ $$aKanoni, S.
000123987 245__ $$aImplicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
000123987 260__ $$c2022
000123987 5060_ $$aAccess copy available to the general public$$fUnrestricted
000123987 5203_ $$aBackground: 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.
000123987 536__ $$9info:eu-repo/grantAgreement/EC/FP7/608765/EU/WILLIAM HARVEY INTERNATIONAL TRANSLATIONAL RESEARCH ACADEMY/WHRI-ACADEMY$$9info:eu-repo/grantAgreement/EC/H2020/786833/EU/GENetics and the Electrocardiogram for predicting Scd rISk/GENESIS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 786833-GENESIS$$9info:eu-repo/grantAgreement/ES/ISCIII/PI17-00142
000123987 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000123987 590__ $$a12.3$$b2022
000123987 592__ $$a9.249$$b2022
000123987 591__ $$aGENETICS & HEREDITY$$b5 / 171 = 0.029$$c2022$$dQ1$$eT1
000123987 593__ $$aCell Biology$$c2022$$dQ1
000123987 591__ $$aBIOTECHNOLOGY & APPLIED MICROBIOLOGY$$b9 / 158 = 0.057$$c2022$$dQ1$$eT1
000123987 593__ $$aGenetics$$c2022$$dQ1
000123987 593__ $$aEcology, Evolution, Behavior and Systematics$$c2022$$dQ1
000123987 594__ $$a25.5$$b2022
000123987 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000123987 700__ $$aGraham, S. E.
000123987 700__ $$aWang, Y.
000123987 700__ $$aSurakka, I.
000123987 700__ $$aRamdas, S.
000123987 700__ $$aZhu, X.
000123987 700__ $$aClarke, S. L.
000123987 700__ $$aBhatti, K. F.
000123987 700__ $$aVedantam, S.
000123987 700__ $$aWinkler, T. W.
000123987 700__ $$aLocke, A. E.
000123987 700__ $$aMarouli, E.
000123987 700__ $$aZajac, G. J. M.
000123987 700__ $$aWu, K.H. H.
000123987 700__ $$aNtalla, I.
000123987 700__ $$aHui, Q.
000123987 700__ $$aKlarin, D.
000123987 700__ $$aHiliard, A.T.
000123987 700__ $$aWang, Z.
000123987 700__ $$aXue, Ch.
000123987 700__ $$aThorleidson, G.
000123987 700__ $$aHelgadottir, A.
000123987 700__ $$aGudbjartsson, D. F.
000123987 700__ $$aHolm, H.
000123987 700__ $$aOlafsson, I.
000123987 700__ $$aHwang, M. Y.: Han, S.
000123987 700__ $$aAkiyama, M.
000123987 700__ $$aSakue, S.
000123987 700__ $$aTerao, S.
000123987 700__ $$aKanai, M.
000123987 700__ $$aZhou, W.
000123987 700__ $$aBrumpton, B. M.
000123987 700__ $$aRasheed, H.
000123987 700__ $$aHavulinna, A. S.
000123987 700__ $$aVeturi, Y.
000123987 700__ $$0(orcid)0000-0003-4130-5866$$aRamírez, J.$$uUniversidad de Zaragoza
000123987 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000123987 773__ $$g23 (2022), 268[42 pp.]$$pGenome Biol.$$tGenome biology$$x1474-7596
000123987 8564_ $$s2235978$$uhttps://zaguan.unizar.es/record/123987/files/texto_completo.pdf$$yVersión publicada
000123987 8564_ $$s2338518$$uhttps://zaguan.unizar.es/record/123987/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000123987 909CO $$ooai:zaguan.unizar.es:123987$$particulos$$pdriver
000123987 951__ $$a2024-03-18-16:57:10
000123987 980__ $$aARTICLE