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11دورية أكاديمية
المؤلفون: Shenkin, SD, Pernet, C, Nichols, TE, Poline, JB, Matthews, PM, van der Lugt, A, Mackay, C, Lanyon, L, Mazoyer, B, Boardman, JP, Thompson, PM, Fox, N, Marcus, DS, Sheikh, A, Cox, SR, Anblagan, D, Job, DE, Dickie, DA, Rodriguez, D, Wardlaw, JM
المصدر: NeuroImage. 153:399-409
مصطلحات موضوعية: Medicin och hälsovetenskap
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12دورية أكاديمية
المؤلفون: Barban, N, Jansen, R, de Vlaming, R, Vaez, A, Mandemakers, JJ, Tropf, FC, Shen, X, Wilson, JF, Chasman, DI, Nolte, IM, Tragante, V, van der Laan, SW, Perry, JRB, Kong, A, Ahluwalia, TS, Albrecht, E, Yerges-Armstrong, L, Atzmon, G, Auro, K, Ayers, K, Bakshi, A, Ben-Avraham, D, Berger, K, Bergman, A, Bertram, L, Bielak, LF, Bjornsdottir, G, Bonder, MJ, Broer, L, Bui, M, Barbieri, C, Cavadino, A, Chavarro, JE, Turman, C, Concas, MP, Cordell, HJ, Davies, G, Eibich, P, Eriksson, N, Esko, T, Eriksson, J, Falahi, F, Felix, JF, Fontana, MA, Franke, L, Gandin, I, Gaskins, AJ, Gieger, C, Gunderson, EP, Guo, XQ, Hayward, C, He, CY, Hofer, E, Huang, HY, Joshi, PK, Kanoni, S, Karlsson, R, Kiechl, S, Kifley, A, Kluttig, A, Kraft, P, Lagou, V, Lecoeur, C, Lahti, J, Li-Gao, RF, Lind, PA, Liu, T, Makalic, E, Mamasoula, C, Matteson, L, Mbarek, H, McArdle, PF, McMahon, G, Meddens, SFW, Mihailov, E, Miller, M, Missmer, SA, Monnereau, C, van der Most, PJ, Myhre, R, Nalls, MA, Nutile, T, Kalafati, IP, Porcu, E, Prokopenko, I, Rajan, KB, Rich-Edwards, J, Rietveld, CA, Robino, A, Rose, LM, Rueedi, R, Ryan, KA, Saba, Y, Schmidt, D, Smith, JA, Stolk, L, Streeten, E, Tonjes, A, Thorleifsson, G, Ulivi, S, Wedenoja, J, Wellmann, J, Willeit, P, Yao, J, Yengo, L, Zhao, JH, Zhao, W, Zhernakova, DV, Amin, N, Andrews, H, Balkau, B, Barzilai, N, Bergmann, S, Biino, G, Bisgaard, H, Bonnelykke, K, Boomsma, DI, Buring, JE, Campbell, H, Cappellani, S, Ciullo, M, Cox, SR, Cucca, F, Toniolo, D, Davey-Smith, G, Deary, IJ, Dedoussis, G, Deloukas, P, van Duijn, CM, de Geus, EJC, Eriksson, JG, Evans, DA, Faul, JD, Sala, CF, Froguel, P, Gasparini, P, Girotto, G, Grabe, HJ, Greiser, KH, Groenen, PJF, de Haan, HG, Haerting, J, Harris, TB, Heath, AC, Heikkila, K, Hofman, A, Homuth, G, Holliday, EG, Hopper, J, Hypponen, E, Jacobsson, B, Jaddoe', VWV, Johannesson, M, Kahonen, M, Kajantie, E, Kardia, SLR, Keavney, B, Kolcic, I, Koponen, P, Kovacs, P, Kronenberg, F, Kutalik, Z, La Bianca, M, Lachance, G, Iacono, WG, Lai, S, Lehtimaki, T, Liewald, DC, Lindgren, CM, Liu, YM, Luben, R, Lucht, M, Luoto, R, Magnus, P, Magnusson, PKE, Martin, NG, McGue, M, McQuillan, R, Medland, SE, Meisinger, C, Mellstrom, D, Metspalu, A, Traglia, M, Milani, L, Mitchell, P, Montgomery, GW, Mook-Kanamori, D, de Mutsert, R, Nohr, EA, Ohlsson, C, Olsen, P, Ong, KK, Paternoster, L, Pattie, A, Penninx, BWJH, Perola, M, Peyser, PA, Pirastu, M, Polasek, O, Power, C, Kaprio, J, Raffel, LJ, Raikkonen, K, Raitakari, O, Ridker, PM, Ring, SM, Roll, K, Rudan, I, Ruggiero, D, Rujescu, D, Salomaa, V, Schlessinger, D, Schmidt, H, Schmidt, R, Schupf, N, Smit, J, Sorice, R, Spector, TD, Starr, JM, Stockl, D, Strauch, K, Stumvoll, M, Swertz, MA, Thorsteinsdottir, U, Thurik, AR, Timpson, NJ, Tung, JY, Uitterlinden, AG, Vaccargiu, S, Viikari, J, Vitart, V, Volzke, H, Vollenweider, P, Vuckovic, D, Waage, J, Wagner, GG, Wang, JJ, Wareham, NJ, Weir, DR, Willemsen, G, Willeit, J, Wright, AF, Zondervan, KT, Stefansson, K, Krueger, RF, Lee, JJ, Benjamin, DJ, Cesarini, D, Koellinger, PD, den Hoed, M, Snieder, H, Mills, MC
المصدر: Nature genetics. 48(12):1462-1472
مصطلحات موضوعية: Medicin och hälsovetenskap
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13دورية أكاديمية
المؤلفون: Stacey, D, Chen, LY, Stanczyk, PJ, Howson, JMM, Mason, AM, Burgess, S, MacDonald, S, Langdown, J, McKinney, H, Downes, K, Farahi, N, Peters, JE, Basu, S, Pankow, JS, Tang, WH, Pankratz, N, Sabater-Lleal, M, de Vries, PS, Smith, NL, Dehghan, A, Heath, AS, Morrison, AC, Reiner, AP, Johnson, A, Richmond, A, Peters, A, Vlieg, AV, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O'Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Conomos, MP, Liu, ML, Brown, MR, Jhun, MA, Chen, MH, de Maat, MPM, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, RF, Damrauer, SM, Cox, SR, Trompet, S, Felix, SB, Volker, U, Koenig, W, Jukema, JW, Guo, XQ, Gelinas, AD, Schneider, DJ, Janjic, N, Samani, NJ, Ye, S, Summers, C, Chilvers, ER, Danesh, J, Paul, DS
المصدر: Nature communications. 13(1):1962
مصطلحات موضوعية: Medicin och hälsovetenskap
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14دورية أكاديمية
المؤلفون: Tin, A, Fohner, AE, Yang, Q, Brody, JA, Davies, G, Yao, J, Liu, D, Caro, I, Lindbohm, JV, Duggan, MR, Meirelles, O, Harris, SE, Gudmundsdottir, V, Taylor, AM, Henry, A, Beiser, AS, Shojaie, A, Coors, A, Fitzpatrick, AL, Langenberg, C, Satizabal, CL, Sitlani, CM, Wheeler, E, Tucker-Drob, EM, Bressler, J, Coresh, J, Bis, JC, Candia, J, Jennings, LL, Pietzner, M, Lathrop, M, Lopez, OL, Redmond, P, Gerszten, RE, Rich, SS, Heckbert, SR, Austin, TR, Hughes, TM, Tanaka, T, Emilsson, V, Vasan, RS, Guo, X, Zhu, Y, Tzourio, C, Rotter, JI, Walker, KA, Ferrucci, L, Kivimäki, M, Breteler, MMB, Cox, SR, Debette, S, Mosley, TH, Gudnason, VG, Launer, LJ, Psaty, BM, Seshadri, S, Fornage, M
المصدر: Communications Biology , 6 (1) , Article 1117. (2023)
مصطلحات موضوعية: Middle Aged, Humans, Aged, Alzheimer Disease, Cognition, Cognitive Dysfunction, Neurons, Biomarkers
الوصف: Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer’s disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.
وصف الملف: text
العلاقة: https://discovery.ucl.ac.uk/id/eprint/10181806/1/s42003-023-05454-1.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10181806Test/
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15دورية أكاديمية
المؤلفون: Saunders, TS, Pozzolo, FE, Heslegrave, A, King, D, McGeachan, RI, Spires-Jones, MP, Harris, SE, Ritchie, C, Muniz-Terrera, G, Deary, IJ, Cox, SR, Zetterberg, H, Spires-Jones, TL
مصطلحات موضوعية: array tomography, cognition, cognitive ageing, plasma biomarkers, western blotting
الوصف: Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer's disease. While these blood biomarkers are promising for distinguishing people with Alzheimer's disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while tau phosphorylated at threonine 181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown. Here, we tested whether plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and fibrillary acidic protein predict cognitive decline between ages 72 and 82 in 195 participants in the Lothian birth cohorts 1936 study of cognitive ageing. We further examined post-mortem brain samples from temporal cortex to determine the distribution of tau phosphorylated at threonine 181 in the brain. Several forms of tau phosphorylated at threonine 181 have been shown to contribute to synapse degeneration in Alzheimer's disease, which correlates closely with cognitive decline in this form of dementia, but to date, there have not been investigations of whether tau phosphorylated at threonine 181 is found in synapses in Alzheimer's disease or healthy ageing brain. It was also previously unclear whether tau phosphorylated at threonine 181 accumulated in dystrophic neurites around plaques, which could contribute to tau leakage to the periphery due to impaired membrane integrity in dystrophies. Brain homogenate and biochemically enriched synaptic fractions were examined with western blot to examine tau phosphorylated at threonine 181 levels between groups (n = 10-12 per group), and synaptic and astrocytic localization of tau phosphorylated at threonine 181 were examined using array tomography (n = 6-15 per group), and localization of tau phosphorylated at threonine 181 in plaque-associated dystrophic neurites with associated gliosis were ...
وصف الملف: fcad113 - ?
العلاقة: Brain Commun; https://qmro.qmul.ac.uk/xmlui/handle/123456789/89809Test
الإتاحة: https://doi.org/10.1093/braincomms/fcad113Test
https://qmro.qmul.ac.uk/xmlui/handle/123456789/89809Test -
16دورية أكاديمية
المؤلفون: Schlosser, P, Tin, A, Matias-Garcia, PR, Thio, CHL, Joehanes, R, Liu, HB, Weihs, A, Yu, Z, Hoppmann, A, Grundner-Culemann, F, Min, JEL, Adeyemo, AA, Agyemang, C, Arnlov, J, Aziz, NA, Baccarelli, A, Bochud, M, Brenner, H, Breteler, MMB, Carmeli, C, Chaker, L, Chambers, JC, Cole, SA, Coresh, J, Corre, T, Correa, A, Cox, SR, de Klein, N, Delgado, GE, Domingo-Relloso, A, Eckardt, KU, Ekici, AB, Endlich, K, Evans, KL, Floyd, JS, Fornage, M, Franke, L, Fraszczyk, E, Gao, X, Ghanbari, M, Ghasemi, S, Gieger, C, Greenland, P, Grove, ML, Harris, SE, Hemani, G, Henneman, P, Herder, C, Horvath, S, Hou, LF, Hurme, MA, Hwang, SJ, Jarvelin, MR, Kardia, SLR, Kasela, S, Kleber, ME, Koenig, W, Kooner, JS, Kramer, H, Kronenberg, F, Kuhnel, B, Lehtimaki, T, Lind, L, Liu, D, Liu, YM, Lloyd-Jones, DM, Lohman, K, Lorkowski, S, Lu, AT, Marioni, RE, Marz, W, McCartney, DL, Meeks, KAC, Milani, L, Mishra, PP, Nauck, M, Navas-Acien, A, Nowak, C, Peters, A, Prokisch, H, Psaty, BM, Raitakari, OT, Ratliff, SM, Reiner, AP, Rosas, SE, Schottker, B, Schwartz, J, Sedaghat, S, Smith, JA, Sotoodehnia, N, Stocker, HR, Stringhini, S, Sundstrom, J, Swenson, BR, Tellez-Plaza, M, van Meurs, JBJ, van Vliet-Ostaptchouk, JV, Venema, A, Verweij, N, Walker, RM, Wielscher, M, Winkelmann, J, Wolffenbuttel, BHR, Zhao, W, Zheng, YN, Loh, M, Snieder, H, Levy, D, Waldenberger, M, Susztak, K, Kottgen, A, Teumer, A
المصدر: Nature communications. 12(1):7174
مصطلحات موضوعية: Medicin och hälsovetenskap
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17دورية أكاديمية
المؤلفون: Tin, A, Schlosser, P, Matias-Garcia, PR, Thio, CHL, Joehanes, R, Liu, HB, Yu, Z, Weihs, A, Hoppmann, A, Grundner-Culemann, F, Min, JEL, Kuhns, VLH, Adeyemo, AA, Agyemang, C, Arnlov, J, Aziz, NA, Baccarelli, A, Bochud, M, Brenner, H, Bressler, J, Breteler, MMB, Carmeli, C, Chaker, L, Coresh, J, Corre, T, Correa, A, Cox, SR, Delgado, GE, Eckardt, KU, Ekici, AB, Endlich, K, Floyd, JS, Fraszczyk, E, Gao, X, Gelber, AC, Ghanbari, M, Ghasemi, S, Gieger, C, Greenland, P, Grove, ML, Harris, SE, Hemani, G, Henneman, P, Herder, C, Horvath, S, Hou, LF, Hurme, MA, Hwang, SJ, Kardia, SLR, Kasela, S, Kleber, ME, Koenig, W, Kooner, JS, Kronenberg, F, Kuhnel, B, Ladd-Acosta, C, Lehtimaki, T, Lind, L, Liu, D, Lloyd-Jones, DM, Lorkowski, S, Lu, AT, Marioni, RE, Marz, W, McCartney, DL, Meeks, KAC, Milani, L, Mishra, PP, Nauck, M, Nowak, C, Peters, A, Prokisch, H, Psaty, BM, Raitakari, OT, Ratliff, SM, Reiner, AP, Schottker, B, Schwartz, J, Sedaghat, S, Smith, JA, Sotoodehnia, N, Stocker, HR, Stringhini, S, Sundstrom, J, Swenson, BR, van Meurs, JBJ, van Vliet-Ostaptchouk, JV, Venema, A, Volker, U, Winkelmann, J, Wolffenbuttel, BHR, Zhao, W, Zheng, YN, Loh, M, Snieder, H, Waldenberger, M, Levy, D, Akilesh, S, Woodward, OM, Susztak, K, Teumer, A, Kottgen, A
المصدر: Nature communications. 12(1):7173
مصطلحات موضوعية: Medicin och hälsovetenskap
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18دورية أكاديمية
المؤلفون: Scherer, SW, Cheung, J, MacDonald, JR, Osborne, LR, Nakabayashi, K, Herbrick, JA, Carson, AR, Parker-Katiraee, L, Skaug, J, Khaja, R, Zhang, JJ, Hudek, AK, Li, M, Haddad, M, Duggan, GE, Fernandez, BA, Kanematsu, E, Gentles, S, Christopoulos, CC, Choufani, S, Kwasnicka, D, Zheng, XQH, Lai, ZW, Nusskern, D, Zhang, Q, Gu, ZP, Lu, F, Zeesman, S, Nowaczyk, MJ, Teshima, I, Chitayat, D, Shuman, C, Weksberg, R, Zackai, EH, Grebe, TA, Cox, SR, Kirkpatrick, SJ, Rahman, N, Friedman, JM, Heng, HHQ, Pelicci, PG, Lo-Coco, F, Belloni, E, Shaffer, LG, Pober, B, Morton, CC, Gusella, JF, Bruns, GAP, Korf, BR, Quade, BJ, Ligon, AH, Ferguson, H, Higgins, AW, Leach, NT, Herrick, SR, Lemyre, E, Farra, CG, Kim, HG, Summers, AM, Gripp, KW, Roberts, W, Szatmari, P, Winsor, EJT, Grzeschik, KH, Teebi, A, Minassian, BA, Kere, J, Armengol, L, Pujana, MA, Estivill, X, Wilson, MD, Koop, BF, Tosi, S, Moore, GE, Boright, AP, Zlotorynski, E, Kerem, B, Kroisel, PM, Petek, E, Oscier, DG, Mould, SJ, Dohner, H, Dohner, K, Rommens, JM, Vincent, JB, Venter, JC, Li, PW, Mural, RJ, Adams, MD, Tsui, LC
المصدر: Science (New York, N.Y.). 300(5620):767-772
مصطلحات موضوعية: Medicin och hälsovetenskap
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19دورية أكاديمية
المؤلفون: Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, Raikkonen, K
الوصف: Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
العلاقة: pii: 10.1038/s41380-022-01710-8; Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N. J., Beiser, A., Bey, K., Bis, J. C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S. R., Davies, G., De Jager, P. L. ,. Raikkonen, K. (2022). Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning. MOLECULAR PSYCHIATRY, 27 (11), pp.4419-4431. https://doi.org/10.1038/s41380-022-01710-8Test.; http://hdl.handle.net/11343/335803Test
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20دورية أكاديمية
المؤلفون: Temprano-Sagrera, G, Sitlani, CM, Bone, WP, Martin-Bornez, M, Voight, BF, Morrison, AC, Damrauer, SM, de Vries, PS, Smith, NL, Sabater-Lleal, M, Krupinksi, J, Dehghan, A, Heath, AS, Reiner, AP, Johnson, A, Richmond, A, Peters, A, van Hylckama Vlieg, A, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O’Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Liu, M, Brown, MR, Conomos, MP, Jhun, MA, Chen, MH, de Maat, MPM, Pankratz, N, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, R, Cox, SR, Trompet, S, Felix, SB, Völker, U, Tang, W, Koenig, W, Jukema, JW, Guo, X, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, de Andrade, M, Brody, JA, Pattee, JW, Haessler, J, Brumpton, BM, Chasman, DI, Suchon, P, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM
الوصف: Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.
وصف الملف: text
العلاقة: https://e-space.mmu.ac.uk/631036Test/; https://doi.org/10.1111/jth.15698Test; https://e-space.mmu.ac.uk/631036/1/Multi-phenotype%20analyses%20of%20hemostatic%20traits%20with%20cardiovascular%20events%20reveal%20novel%20genetic%20associations.pdfTest; Temprano-Sagrera, G , Sitlani, CM , Bone, WP , Martin-Bornez, M , Voight, BF , Morrison, AC , Damrauer, SM , de Vries, PS , Smith, NL , Sabater-Lleal, M , Krupinksi, J , Dehghan, A , Heath, AS , Morrison, AC , Reiner, AP , Johnson, A , Richmond, A , Peters, A , van Hylckama Vlieg, A , McKnight, B , Psaty, BM , Hayward, C , Ward-Caviness, C , O’Donnell, C , Chasman, D , Strachan, DP , Tregouet, DA , Mook-Kanamori, D , Gill, D , Thibord, F , Asselbergs, FW , Leebeek, FWG , Rosendaal, FR , Davies, G , Homuth, G , Temprano, G , Campbell, H , Taylor, HA , Bressler, J , Huffman, JE , Rotter, JI , Yao, J , Wilson, JF , Bis, JC , Hahn, JM , Desch, KC , Wiggins, KL , Raffield, LM , Bielak, LF , Yanek, LR , Kleber, ME , Mueller, M , Kavousi, M , Mangino, M , Liu, M , Brown, MR , Conomos, MP , Jhun, MA , Chen, MH , de Maat, MPM , Pankratz, N , Peyser, PA , Elliot, P , Wei, P , Wild, PS , Morange, PE , van der Harst, P , Yang, Q , Le, NQ , Marioni, R , Li, R , Damrauer, SM , Cox, SR , Trompet, S , Felix, SB , Völker, U , Tang, W , Koenig, W , Jukema, JW , Guo, X , Lindstrom, S , Wang, L , Smith, EN , Gordon, W , van Hylckama Vlieg, A , de Andrade, M , Brody, JA , Pattee, JW , Haessler, J , Brumpton, BM , Chasman, DI , Suchon, P , Chen, MH , Turman, C , Germain, M , Wiggins, KL , MacDonald, J , Braekkan, SK , Armasu, SM and Pankratz, N (2022) Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations. Journal of Thrombosis and Haemostasis, 20 (6). pp. 1331-1349. ISSN 1538-7933
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