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11دورية أكاديمية
المؤلفون: Schnitzler, Johan G, Hoogeveen, Renate M, Ali, Lubna, Prange, Koen HM, Waissi, Farahnaz, van Weeghel, Michel, Bachmann, Julian C, Versloot, Miranda, Borrelli, Matthew J, Yeang, Calvin, De Kleijn, Dominique PV, Houtkooper, Riekelt H, Koschinsky, Marlys L, de Winther, Menno PJ, Groen, Albert K, Witztum, Joseph L, Tsimikas, Sotirios, Stroes, Erik SG, Kroon, Jeffrey
المصدر: Circulation Research. 126(10)
مصطلحات موضوعية: Cardiovascular, Atherosclerosis, 2.1 Biological and endogenous factors, Aetiology, Aged, Aged, 80 and over, Animals, Apolipoprotein B-100, Apolipoproteins A, Cells, Cultured, Coculture Techniques, Disease Models, Animal, Endothelial Cells, Female, Glycolysis, Humans, Inflammation Mediators, Intercellular Adhesion Molecule-1, Leukocytes, Lipoprotein(a), Male, Mice, Transgenic, Middle Aged, Mutation, Oligonucleotides, Antisense, Phosphofructokinase-2, Receptors, LDL, Transendothelial and Transepithelial Migration, endothelial cell, glycolysis, inflammation, lipoprotein(a), metabolism, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
الوصف: RationalePatients with elevated levels of lipoprotein(a) [Lp(a)] are hallmarked by increased metabolic activity in the arterial wall on positron emission tomography/computed tomography, indicative of a proinflammatory state.ObjectiveWe hypothesized that Lp(a) induces endothelial cell inflammation by rewiring endothelial metabolism.Methods and resultsWe evaluated the impact of Lp(a) on the endothelium and describe that Lp(a), through its oxidized phospholipid content, activates arterial endothelial cells, facilitating increased transendothelial migration of monocytes. Transcriptome analysis of Lp(a)-stimulated human arterial endothelial cells revealed upregulation of inflammatory pathways comprising monocyte adhesion and migration, coinciding with increased 6-phophofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)-3-mediated glycolysis. ICAM (intercellular adhesion molecule)-1 and PFKFB3 were also found to be upregulated in carotid plaques of patients with elevated levels of Lp(a). Inhibition of PFKFB3 abolished the inflammatory signature with concomitant attenuation of transendothelial migration.ConclusionsCollectively, our findings show that Lp(a) activates the endothelium by enhancing PFKFB3-mediated glycolysis, leading to a proadhesive state, which can be reversed by inhibition of glycolysis. These findings pave the way for therapeutic agents targeting metabolism aimed at reducing inflammation in patients with cardiovascular disease.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/3xc2z31wTest
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12دورية أكاديمية
المؤلفون: Buono, Michele F, Benavente, Ernest Diez, Slenders, Lotte, Methorst, Daisey, Tessels, Daniëlle, Mili, Eloi, Finger, Roxy, Kapteijn, Daniek, Daniels, Mark, van den Dungen, Noortje A M, Calis, Jorg J A, Mol, Barend M, de Borst, Gert J, de Kleijn, Dominique P V, Pasterkamp, Gerard, den Ruijter, Hester M, Mokry, Michal
المساهمون: Experimentele Afd. Cardiologie 1, CDL Onderzoek Pasterkamp, CDL Research analisten, Cancer, Immuno/reuma onderzoek 1 (Vastert), Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Infection & Immunity, Centraal Diagnostisch Laboratorium, Onderzoek Vrouw Hart & Vaatziekten, Child Health
مصطلحات موضوعية: disease modeling, myofibroblast, phenotypic modulation, plaque cells, smooth muscle cell, Cardiology and Cardiovascular Medicine
الوصف: Background Plaque myofibroblasts are critical players in the initiation and advancement of atherosclerotic disease. They are involved in the production of extracellular matrix, the formation of the fibrous cap, and the underlying lipidic core via modulation processes in response to different environmental cues. Despite clear phenotypic differences between myofibroblast cells and healthy vascular smooth muscle cells, smooth muscle cells are still widely used as a cellular model in atherosclerotic research. Methods and Results Here, we present a conditioned outgrowth method to isolate and culture myofibroblast cells from plaques. We obtained these cells from 27 donors (24 carotid and 3 femoral endarterectomies). We show that they keep their proliferative capacity for 8 passages, are transcriptionally stable, retain donor-specific gene expression programs, and express extracellular matrix proteins (FN1, COL1A1, and DCN) and smooth muscle cell markers (ACTA2, MYH11, and CNN1). Single-cell transcriptomics reveals that the cells in culture closely resemble the plaque myofibroblasts. Chromatin immunoprecipitation sequencing shows the presence of histone H3 lysine 4 dimethylation at the MYH11 promoter, pointing to their smooth muscle cell origin. Finally, we demonstrated that plaque myofibroblasts can be efficiently transduced (>97%) and are capable of taking up oxidized low-density lipoprotein and undergoing calcification. Conclusions In conclusion, we present a method to isolate and culture cells that retain plaque myofibroblast phenotypical and functional capabilities, making them a suitable in vitro model for studying selected mechanisms of atherosclerosis.
وصف الملف: application/pdf
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13دورية أكاديمية
المؤلفون: Mekke, Joost M, Sakkers, Tim R, Verwer, Maarten C, van den Dungen, Noortje A M, Song, Yipei, Miller, Clint L, Finn, Aloke V, Pasterkamp, Gerard, Mokry, Michal, den Ruijter, Hester M, Vink, Aryan, de Kleijn, Dominique P V, de Borst, Gert J, Haitjema, Saskia, van der Laan, Sander W
المساهمون: Zorgeenheid Vaatchirurgie Medisch, Experimentele Afd. Cardiologie 1, Circulatory Health, CDL Research analisten, Cancer, CDL Onderzoek Pasterkamp, Centraal Diagnostisch Laboratorium, Child Health, Onderzoek Vrouw Hart & Vaatziekten, Pathologie Pathologen staf, Infection & Immunity, Regenerative Medicine and Stem Cells, CDL Cluster Speciële Diagnostiek
مصطلحات موضوعية: Calcinosis/pathology, Carotid Arteries/pathology, Carotid Stenosis/pathology, Collagen, Erythrocyte Membrane/pathology, Female, Glycophorins, Hemorrhage/pathology, Humans, Lipids, Magnetic Resonance Imaging, Male, Plaque, Atherosclerotic/pathology, General, Journal Article, Research Support, Non-U.S. Gov't
الوصف: The accumulation of erythrocyte membranes within an atherosclerotic plaque may contribute to the deposition of free cholesterol and thereby the enlargement of the necrotic core. Erythrocyte membranes can be visualized and quantified in the plaque by immunostaining for the erythrocyte marker glycophorin C. Hence, we theorized that the accumulation of erythrocytes quantified by glycophorin C could function as a marker for plaque vulnerability, possibly reflecting intraplaque hemorrhage (IPH), and offering predictive value for pre-procedural neurological symptoms. We employed the CellProfiler-integrated slideToolKit workflow to visualize and quantify glycophorin C, defined as the total plaque area that is positive for glycophorin C, in single slides of culprit lesions obtained from the Athero-Express Biobank of 1819 consecutive asymptomatic and symptomatic patients who underwent carotid endarterectomy. Our assessment included the evaluation of various parameters such as lipid core, calcifications, collagen content, SMC content, and macrophage burden. These parameters were evaluated using a semi-quantitative scoring method, and the resulting data was dichotomized as predefined criteria into categories of no/minor or moderate/heavy staining. In addition, the presence or absence of IPH was also scored. The prevalence of IPH and pre-procedural neurological symptoms were 62.4% and 87.1%, respectively. The amount of glycophorin staining was significantly higher in samples from men compared to samples of women (median 7.15 (IQR:3.37, 13.41) versus median 4.06 (IQR:1.98, 8.32), p < 0.001). Glycophorin C was associated with IPH adjusted for clinical confounders (OR 1.90; 95% CI 1.63, 2.21; p = < 0.001). Glycophorin C was significantly associated with ipsilateral pre-procedural neurological symptoms (OR:1.27, 95%CI:1.06-1.41, p = 0.005). Sex-stratified analysis, showed that this was also the case for men (OR 1.37; 95%CI 1.12, 1.69; p = 0.003), but not for women (OR 1.15; 95%CI 0.77, 1.73; p = 0.27). Glycophorin C was ...
وصف الملف: application/pdf
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14دورية أكاديمية
المؤلفون: Benavente, Ernest Diez, Karnewar, Santosh, Buono, Michele, Mili, Eloi, Hartman, Robin J G, Kapteijn, Daniek, Slenders, Lotte, Daniels, Mark, Aherrahrou, Redouane, Reinberger, Tobias, Mol, Barend M, de Borst, Gert J, de Kleijn, Dominique P V, Prange, Koen H M, Depuydt, Marie A C, de Winther, Menno P J, Kuiper, Johan, Björkegren, Johan L M, Erdmann, Jeanette, Civelek, Mete, Mokry, Michal, Owens, Gary K, Pasterkamp, Gerard, den Ruijter, Hester M
المساهمون: Experimentele Afd. Cardiologie 1, Circulatory Health, Zorgeenheid Vaatchirurgie Medisch, Regenerative Medicine and Stem Cells, Infection & Immunity, CDL Onderzoek Pasterkamp, Child Health, Centraal Diagnostisch Laboratorium, Onderzoek Vrouw Hart & Vaatziekten
مصطلحات موضوعية: coronary artery disease, gene expression, lipids, plaque, women's health, Cardiology and Cardiovascular Medicine
الوصف: BACKGROUND: Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. METHODS: Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male Apoe -/- mice fed a Western diet for 18 and 30 weeks. RESULTS: Here, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene MFGE8 (milk fat globule EGF and factor V/VIII domain containing) showed retained expression in advanced plaques from female mice but was downregulated in male mice during atherosclerosis progression. CONCLUSIONS: Female atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs.
وصف الملف: application/pdf
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15دورية أكاديمية
المؤلفون: Buono, Michele F, Benavente, Ernest Diez, Daniels, Mark, Mol, Barend M, Mekke, Joost M, de Borst, Gert J, de Kleijn, Dominique P V, van der Laan, Sander W, Pasterkamp, Gerard, Onland-Moret, Charlotte, Mokry, Michal, den Ruijter, Hester M
المساهمون: Experimentele Afd. Cardiologie 1, Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Infection & Immunity, CDL Onderzoek Pasterkamp, Centraal Diagnostisch Laboratorium, Cardiovasculaire Epi Team 3, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Child Health, Onderzoek Vrouw Hart & Vaatziekten
مصطلحات موضوعية: Atherosclerosis, Carotid, Peripheral, Sex-differences, Vascular, XCI skewing, Endocrinology, Gender Studies
الوصف: BACKGROUND AND AIM: Sex differences in atherosclerosis have been described with female plaques being mostly perceived as stable and fibrous. Sex-specific mechanisms such as mosaic loss of the Y chromosome in men have been linked to cardiovascular health. In women, X-linked mechanisms such as X chromosome inactivation (XCI) skewing is common in several tissues. Yet, information on the role of XCI in female atherosclerotic plaques is lacking. Here, we investigated the presence of XCI skewing in advanced atherosclerotic lesions and its association with cardiovascular risk factors, histological plaque data, and clinical data. METHODS: XCI skewing was quantified in 154 atherosclerotic plaque and 55 blood DNA samples of women included in the Athero-Express study. The skewing status was determined performing the HUMARA assay. Then, we studied the relationship of XCI skewing in female plaque and cardiovascular risk factors using regression models. In addition, we studied if plaque XCI predicted plaque composition, and adverse events during 3-years follow-up using Cox proportional hazard models. RESULTS: XCI skewing was detected in 76 of 154 (49.4%) plaques and in 27 of 55 (67%) blood samples. None of the clinical risk factors were associated with plaque skewing. Plaque skewing was more often detected in plaques with a plaque hemorrhage (OR [95% CI]: 1.44 [1.06-1.98], P = 0.02). Moreover, skewed plaques were not associated with a higher incidence of composite and major events but were specifically associated with peripheral artery events during a 3-year follow-up period in a multivariate model (HR [95%CI]: 1.46 [1.09-1.97]; P = 0.007). CONCLUSIONS: XCI skewing is common in carotid plaques of females and is predictive for the occurrence of peripheral artery events within 3 years after carotid endarterectomy.
وصف الملف: application/pdf
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16دورية أكاديمية
المؤلفون: Overmars, L. Malin, Mekke, Joost M., van Solinge, Wouter W., De Jager, Saskia C.A., Hulsbergen-Veelken, Cornelia A.R., Hoefer, Imo E., de Kleijn, Dominique P.V., de Borst, Gert J., van der Laan, Sander W., Haitjema, Saskia
المساهمون: CDL Upod, Zorgeenheid Vaatchirurgie Medisch, Centraal Diagnostisch Laboratorium, Experimental Cardiology Laboratory, Experimentele Afd. Cardiologie 2, Circulatory Health, Infection & Immunity, Regenerative Medicine and Stem Cells, CDL Onderzoek Pasterkamp, CDL Cluster Speciële Diagnostiek
مصطلحات موضوعية: Blood cell characteristics, Carotid endarterectomy, Hematology, Inflammation, Intraplaque hemorrhage, Machine learning, Major adverse cardiovascular events, Routine care data, Internal Medicine, Cardiology and Cardiovascular Medicine, Journal Article
الوصف: BACKGROUND AND AIMS: Patients who underwent carotid endarterectomy (CEA) still have a residual risk of 13% of developing a major adverse cardiovascular event (MACE) within 3 years. Inflammatory processes leading up to MACE are not fully understood. Therefore, we examined blood cell characteristics (BCCs), possibly reflecting inflammatory processes, in relation to MACE to identify BCCs that may contribute to an increased risk. METHODS: We analyzed 75 pretreatment BCCs from the Sapphire analyzer, and clinical data from the Athero-Express biobank in relation to MACE after CEA using Random Survival Forests, and a Generalized Additive Survival Model. To understand biological mechanisms, we related the identified variables to intraplaque hemorrhage (IPH). RESULTS: Of 783 patients, 97 (12%) developed MACE within 3 years after CEA. Red blood cell distribution width (RDW) (HR 1.23 [1.02, 1.68], p = 0.022), CV of lymphocyte size (LACV) (HR 0.78 [0.63, 0.99], p = 0.043), neutrophil complexity of the intracellular structure (NIMN) (HR 0.80 [0.64, 0.98], p = 0.033), mean neutrophil size (NAMN) (HR 0.67 [0.55, 0.83], p < 0.001), mean corpuscular volume (MCV) (HR 1.35 [1.09, 1.66], p = 0.005), eGFR (HR 0.65 [0.52, 0.80], p < 0.001); and HDL-cholesterol (HR 0.62 [0.45, 0.85], p = 0.003) were related to MACE. NAMN was related to IPH (OR 0.83 [0.71-0.98], p = 0.02). CONCLUSIONS: This is the first study to present a higher RDW and MCV and lower LACV, NIMN and NAMN as biomarkers reflecting inflammatory processes that may contribute to an increased risk of MACE after CEA.
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17دورية أكاديمية
المؤلفون: Verwer, Maarten C., Mekke, Joost, Timmerman, Nathalie, Waissi, Farahnaz, Boltjes, Arjan, Pasterkamp, Gerard, de Borst, Gert J., de Kleijn, Dominique P.V.
المساهمون: Zorgeenheid Vaatchirurgie Medisch, CDL Cluster Onderzoek en Onderwijs, Centraal Diagnostisch Laboratorium, Circulatory Health, Regenerative Medicine and Stem Cells, Infection & Immunity
مصطلحات موضوعية: General
الوصف: Extracellular vesicles (EV) are a novel biomarker source for diagnosis and prognosis of cardiovascular disease. A protein comparison of plasma EVs in relation to blood plasma and atherosclerotic plaque has not been performed but would provide insight into the origin and content of biomarker sources and their association with atherosclerotic progression. Using samples of 88 carotid endarterectomy patients in the Athero-Express, 92 proteins (Olink Cardiovascular III panel) were measured in citrate plasma, plasma derived LDL-EVs and atherosclerotic plaque. Proteins were correlated between sources and were related to pre-operative stroke and 3-year major adverse cardiovascular events (MACE). Plasma and EV proteins correlated moderately on average, but with substantial variability. Both showed little correlation with plaque, suggesting that these circulating biomarkers may not originate from the latter. Plaque (n = 17) contained most differentially-expressed proteins in patients with stroke, opposed to EVs (n = 6) and plasma (n = 5). In contrast, EVs contained most differentially-expressed proteins for MACE (n = 21) compared to plasma (n = 9) and plaque (n = 1). EVs appear to provide additional information about severity and progression of systemic atherosclerosis than can be obtained from plasma or atherosclerotic plaque.
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18دورية أكاديمية
المؤلفون: Song, Yipei, Cisternino, Francesco, Mekke, Joost M, de Borst, Gert J, de Kleijn, Dominique P V, Pasterkamp, Gerard, Vink, Aryan, Glastonbury, Craig A, van der Laan, Sander W, Miller, Clint L
المساهمون: Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Infection & Immunity, Centraal Diagnostisch Laboratorium, Pathologie Pathologen staf, CDL Onderzoek Pasterkamp
مصطلحات موضوعية: Entropy, Histological Techniques, Humans, Image Processing, Computer-Assisted/methods, Machine Learning, Plaque, Atherosclerotic/diagnostic imaging, General, Journal Article
الوصف: Tissue segmentation of histology whole-slide images (WSI) remains a critical task in automated digital pathology workflows for both accurate disease diagnosis and deep phenotyping for research purposes. This is especially challenging when the tissue structure of biospecimens is relatively porous and heterogeneous, such as for atherosclerotic plaques. In this study, we developed a unique approach called 'EntropyMasker' based on image entropy to tackle the fore- and background segmentation (masking) task in histology WSI. We evaluated our method on 97 high-resolution WSI of human carotid atherosclerotic plaques in the Athero-Express Biobank Study, constituting hematoxylin and eosin and 8 other staining types. Using multiple benchmarking metrics, we compared our method with four widely used segmentation methods: Otsu's method, Adaptive mean, Adaptive Gaussian and slideMask and observed that our method had the highest sensitivity and Jaccard similarity index. We envision EntropyMasker to fill an important gap in WSI preprocessing, machine learning image analysis pipelines, and enable disease phenotyping beyond the field of atherosclerosis.
وصف الملف: application/pdf
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19دورية أكاديمية
المؤلفون: Kanoni, Stavroula, Graham, Sarah E., Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L., Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J.M., Wu, Kuan Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, Qi Ping, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing Hua, Matsuda, Fumihiko, Jang, Hye Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A., Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Hwu, Chii Min, Hung, Yi Jen, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, EWarwick W., Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Vazquez-Moreno, Miguel, Feitosa, Mary F., Wojczynski, Mary K., Wang, Zhe, Preuss, Michael H., Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Tsao, Noah L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Bayyana, Swati, Stringham, Heather M., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han Na, Ryu, Seungho, Timmers, Paul R.H.J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R.B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih Yi, Wang, Jun Sing, Couture, Christian, Lyytikäinen, Leo Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W.J., Shu, Xiao Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian Min, Koh, Woon Puay, Rhee, Sang Youl, Woo, Jeong Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L.R., Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer Yuarn, Zheng, Wei, Hollander, Anneke Iden, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Costanzo, Maria C., Jang, Dongkeun, Burtt, Noël P., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong S., van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl Heinz, McCarthy, Mark I., Palmer, Colin N.A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean Claude, Lettre, Guillaume, Hart, Leen M.‘t, Elders, Petra J.M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J.F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus A.L.M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee Ming, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching Yu, Wong, Tien Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K.E., Boomsma, Dorret I., Willemsen, Allegonda H.M., Cupples, LAdrienne A., van Meurs, Joyce B.J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, YEugene E., Ho, Yuk Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter W.F., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Mohlke, Karen L., Sun, Yan V., Morris, Andrew P., Boehnke, Michael, Brown, Christopher D., Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J., Assimes, Themistocles L., Peloso, Gina M.
المساهمون: Medicum, Institute for Molecular Medicine Finland, Complex Disease Genetics, Samuli Olli Ripatti / Principal Investigator, HUSLAB, Epigenetics of Complex Diseases and Traits, Department of Medicine, Helsinki University Hospital Area, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Faculty Common Matters (Faculty of Social Sciences), Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation
مصطلحات موضوعية: Cholesterol, Genetics, Genome-wide association study, GWAS, Lipids, 1184 Genetics, developmental biology, physiology, 3142 Public health care science, environmental and occupational health, 3141 Health care science, 112 Statistics and probability
الوصف: 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. ; Peer reviewed
وصف الملف: application/pdf
العلاقة: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.; Kanoni , S , Graham , S E , Wang , Y , Surakka , I , Ramdas , S , Zhu , X , Clarke , S L , Bhatti , K F , Vedantam , S , Winkler , T W , Locke , A E , Marouli , E , Zajac , G J M , Wu , K H H , Ntalla , I , Hui , Q , Klarin , D , Hilliard , A T , Wang , Z , Xue , C , Thorleifsson , G , Helgadottir , A , Gudbjartsson , D F , Holm , H , Olafsson , I , Hwang , M Y , Han , S , Akiyama , M , Sakaue , S , Terao , C , Kanai , M , Zhou , W , Brumpton , B M , Rasheed , H , Havulinna , A S , Veturi , Y , Pacheco , J A , Rosenthal , E A , Lingren , T , Feng , Q P , Kullo , I J , Narita , A , Takayama , J , Martin , H C , Hunt , K A , Trivedi , B , Haessler , J , Giulianini , F , Bradford , Y , Miller , J E , Campbell , A , Lin , K , Millwood , I Y , Rasheed , A , Hindy , G , Faul , J D , Zhao , W , Weir , D R , Turman , C , Huang , H , Graff , M , Choudhury , A , Sengupta , D , Mahajan , A , Brown , M R , Zhang , W , Yu , K , Schmidt , E M , Pandit , A , Gustafsson , S , Yin , X , Luan , J , Zhao , J H , Matsuda , F , Jang , H M , Yoon , K , Medina-Gomez , C , Pitsillides , A , Hottenga , J J , Wood , A R , Ji , Y , Gao , Z , Haworth , S , Yousri , N A , Mitchell , R E , Chai , J F , Aadahl , M , Bjerregaard , A A , Yao , J , Manichaikul , A , Hwu , C M , Hung , Y J , Warren , H R , Ramirez , J , Bork-Jensen , J , Kårhus , L L , Goel , A , Sabater-Lleal , M , Noordam , R , Mauro , P , Matteo , F , McDaid , A F , Marques-Vidal , P , Wielscher , M , Trompet , S , Sattar , N , Møllehave , L T , Munz , M , Zeng , L , Huang , J , Yang , B , Poveda , A , Kurbasic , A , Lamina , C , Forer , L , Scholz , M , Galesloot , T E , Bradfield , J P , Ruotsalainen , S E , Daw , EW W , Zmuda , J M , Mitchell , J S , Fuchsberger , C , Christensen , H , Brody , J A , Vazquez-Moreno , M , Feitosa , M F , Wojczynski , M K , Wang , Z , Preuss , M H , Mangino , M , Christofidou , P , Verweij , N , Benjamins , J W , Engmann , J , Tsao , N L , Verma , A , Slieker , R C , Lo , K S , Zilhao , N R , Le , P , Kleber , M E , Delgado , G E , Huo , S , Ikeda , D D , Iha , H , Yang , J , Liu , J , Demirkan , A , Leonard , H L , Marten , J , Frank , M , Schmidt , B , Smyth , L J , Cañadas-Garre , M , Wang , C , Nakatochi , M , Wong , A , Hutri-Kähönen , N , Sim , X , Xia , R , Huerta-Chagoya , A , Fernandez-Lopez , J C , Lyssenko , V , Nongmaithem , S S , Bayyana , S , Stringham , H M , Irvin , M R , Oldmeadow , C , Kim , H N , Ryu , S , Timmers , P R H J , Arbeeva , L , Dorajoo , R , Lange , L A , Prasad , G , Lorés-Motta , L , Pauper , M , Long , J , Li , X , Theusch , E , Takeuchi , F , Spracklen , C N , Loukola , A , Bollepalli , S , Warner , S C , Wang , Y X , Wei , W B , Nutile , T , Ruggiero , D , Sung , Y J , Chen , S , Liu , F , Yang , J , Kentistou , K A , Banas , B , Nardone , G G , Meidtner , K , Bielak , L F , Smith , J A , Hebbar , P , Farmaki , A E , Hofer , E , Lin , M , Concas , M P , Vaccargiu , S , van der Most , P J , Pitkänen , N , Cade , B E , van der Laan , S W , Chitrala , K N , Weiss , S , Bentley , A R , Doumatey , A P , Adeyemo , A A , Lee , J Y , Petersen , E R B , Nielsen , A A , Choi , H S , Nethander , M , Freitag-Wolf , S , Southam , L , Rayner , N W , Wang , C A , Lin , S Y , Wang , J S , Couture , C , Lyytikäinen , L P , Nikus , K , Cuellar-Partida , G , Vestergaard , H , Hidalgo , B , Giannakopoulou , O , Cai , Q , Obura , M O , van Setten , J , Li , X , Liang , J , Tang , H , Terzikhan , N , Shin , J H , Jackson , R D , Reiner , A P , Martin , L W , Chen , Z , Li , L , Kawaguchi , T , Thiery , J , Bis , J C , Launer , L J , Li , H , Nalls , M A , Raitakari , O T , Ichihara , S , Wild , S H , Nelson , C P , Campbell , H , Jäger , S , Nabika , T , Al-Mulla , F , Niinikoski , H , Braund , P S , Kolcic , I , Kovacs , P , Giardoglou , T , Katsuya , T , de Kleijn , D , de Borst , G J , Kim , E K , Adams , H H H , Ikram , M A , Zhu , X , Asselbergs , F W , Kraaijeveld , A O , Beulens , J W J , Shu , X O , Rallidis , L S , Pedersen , O , Hansen , T , Mitchell , P , Hewitt , A W , Kähönen , M , Pérusse , L , Bouchard , C , Tönjes , A , Chen , Y D I , Pennell , C E , Mori , T A , Lieb , W , Franke , A , Ohlsson , C , Mellström , D , Cho , Y S , Lee , H , Yuan , J M , Koh , W P , Rhee , S Y , Woo , J T , Heid , I M , Stark , K J , Zimmermann , M E , Völzke , H , Homuth , G , Evans , M K , Zonderman , A B , Polasek , O , Pasterkamp , G , Hoefer , I E , Redline , S , Pahkala , K , Oldehinkel , A J , Snieder , H , Biino , G , Schmidt , R , Schmidt , H , Bandinelli , S , Dedoussis , G , Thanaraj , T A , Kardia , S L R , Peyser , P A , Kato , N , Schulze , M B , Girotto , G , Böger , C A , Jung , B , Joshi , P K , Bennett , D A , De Jager , P L , Lu , X , Mamakou , V , Brown , M , Caulfield , M J , Munroe , P B , Guo , X , Ciullo , M , Jonas , J B , Samani , N J , Kaprio , J , Pajukanta , P , Tusié-Luna , T , Aguilar-Salinas , C A , Adair , L S , Bechayda , S A , de Silva , H J , Wickremasinghe , A R , Krauss , R M , Wu , J Y , Zheng , W , Hollander , A I , Bharadwaj , D , Correa , A , Wilson , J G , Lind , L , Heng , C K , Nelson , A E , Golightly , Y M , Wilson , J F , Penninx , B , Kim , H L , Attia , J , Scott , R J , Rao , D C , Arnett , D K , Hunt , S C , Walker , M , Koistinen , H A , Chandak , G R , Mercader , J M , Costanzo , M C , Jang , D , Burtt , N P , Villalpando , C G , Orozco , L , Fornage , M , Tai , ES S , van Dam , R M , Lehtimäki , T , Chaturvedi , N , Yokota , M , Liu , J , Reilly , D F , McKnight , A J , Kee , F , Jöckel , K H , McCarthy , M I , Palmer , C N A , Vitart , V , Hayward , C , Simonsick , E , van Duijn , C M , Jin , Z B , Qu , J , Hishigaki , H , Lin , X , März , W , Gudnason , V , Tardif , J C , Lettre , G , Hart , L M , Elders , P J M , Damrauer , S M , Kumari , M , Kivimaki , M , van der Harst , P , Spector , T D , Loos , R J F , Province , M A , Parra , E J , Cruz , M , Psaty , B M , Brandslund , I , Pramstaller , P P , Rotimi , C N , Christensen , K , Ripatti , S , Widén , E , Hakonarson , H , Grant , S F A , Kiemeney , L A L M , de Graaf , J , Loeffler , M , Kronenberg , F , Gu , D , Erdmann , J , Schunkert , H , Franks , P W , Linneberg , A , Jukema , J W , Khera , A V , Männikkö , M , Jarvelin , M R , Kutalik , Z , Francesco , C , Mook-Kanamori , D O , van Dijk , K W , Watkins , H , Strachan , D P , Grarup , N , Sever , P , Poulter , N , Chuang , L M , Rotter , J I , Dantoft , T M , Karpe , F , Neville , M J , Timpson , N J , Cheng , C Y , Wong , T Y , Khor , C C , Li , H , Sabanayagam , C , Peters , A , Gieger , C , Hattersley , A T , Pedersen , N L , Magnusson , P K E , Boomsma , D I , Willemsen , A H M , Cupples , LA A , van Meurs , J B J , Ghanbari , M , Gordon-Larsen , P , Huang , W , Kim , Y J , Tabara , Y , Wareham , N J , Langenberg , C , Zeggini , E , Kuusisto , J , Laakso , M , Ingelsson , E , Abecasis , G , Chambers , J C , Kooner , J S , de Vries , P S , Morrison , A C , Hazelhurst , S , Ramsay , M , North , K E , Daviglus , M , Kraft , P , Martin , N G , Whitfield , J B , Abbas , S , Saleheen , D , Walters , R G , Holmes , M V , Black , C , Smith , B H , Baras , A , Justice , A E , Buring , J E , Ridker , P M , Chasman , D I , Kooperberg , C , Tamiya , G , Yamamoto , M , van Heel , D A , Trembath , R C , Wei , W Q , Jarvik , G P , Namjou , B , Hayes , M G , Ritchie , M D , Jousilahti , P , Salomaa , V , Hveem , K , Åsvold , B O , Kubo , M , Kamatani , Y , Okada , Y , Murakami , Y , Kim , B J , Thorsteinsdottir , U , Stefansson , K , Zhang , J , Chen , YE E , Ho , Y L , Lynch , J A , Rader , D J , Tsao , P S , Chang , K M , Cho , K , O’Donnell , C J , Gaziano , J M , Wilson , P W F , Frayling , T M , Hirschhorn , J N , Kathiresan , S , Mohlke , K L , Sun , Y V , Morris , A P , Boehnke , M , Brown , C D , Natarajan , P , Deloukas , P , Willer , C J , Assimes , T L & Peloso , G M 2022 , ' Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis ' , Genome Biology , vol. 23 , no. 1 , 268 . https://doi.org/10.1186/s13059-022-02837-1Test; ORCID: /0000-0001-7870-070X/work/130600781; ORCID: /0000-0003-0542-5967/work/130601174; ORCID: /0000-0002-8773-7149/work/130605566; 85144774123; 73609295-cdc2-4438-a33f-d480ed37cb6d; http://hdl.handle.net/10138/355889Test
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20دورية أكاديمية
المؤلفون: van Laarhoven, Constance J. H. C. M., Arnold, Marcel, Danilova, Maria, Dreval, Marina, Ferrari, Elena, Simonetti, Barbara Goeggel, Gralla, Jan, Heldner, Mirjam R., Kalashnikova, Ludmila, Mancuso, Michelangelo, Metso, Tiina M., Steinsiepe, Valentin K, Strbian, Daniel, Tatlisumak, Turgut, de Kleijn, Dominique P. V., de Borst, Gert J
المساهمون: HUS Neurocenter, Neurologian yksikkö, Department of Neurosciences
مصطلحات موضوعية: 3126 Surgery, anesthesiology, intensive care, radiology
الوصف: Peer reviewed
وصف الملف: application/pdf
العلاقة: van Laarhoven , C J H C M , Arnold , M , Danilova , M , Dreval , M , Ferrari , E , Simonetti , B G , Gralla , J , Heldner , M R , Kalashnikova , L , Mancuso , M , Metso , T M , Steinsiepe , V K , Strbian , D , Tatlisumak , T , de Kleijn , D P V & de Borst , G J 2022 , ' Delayed Development of Aneurysmal Dilatations in Patients with Extracranial Carotid Artery Dissections ' , European Journal of Vascular and Endovascular Surgery , vol. 64 , no. 6 , pp. 595-601 . https://doi.org/10.1016/j.ejvs.2022.08.010Test; 7fd84595-b748-4eed-8532-79229e610a71; http://hdl.handle.net/10138/354600Test; 000913368300002
النص الكامل