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3. Experimental Investigation of Lung Toxicity after Radiation Therapy Combined with Immune Checkpoint Inhibitors

Author

Rotgerink, L. Lansink, primary, Burkhardt, R., additional, Groll, T., additional, Felchle, H., additional, Nefzger, S.M., additional, Walther, C.N., additional, Gissibl, J., additional, Timnik, V.R., additional, Dobiasch, S., additional, Steiger, K., additional, Combs, S.E., additional, Wilkens, J., additional, and Fischer, J., additional

Published
2023
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7. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Author

Schillemans, T., Tragante, V., Maitusong, B., Gigante, B., Cresci, S., Laguzzi, F., Vikstrom, M., Richards, M., Pilbrow, A., Cameron, V., Foco, L., Doughty, R.N., Kuukasjarvi, P., Allayee, H., Hartiala, J.A., Tang, W.H.W., Lyytikainen, L.P., Nikus, K., Laurikka, J.O., Srinivasan, S., Mordi, I.R., Trompet, S., Kraaijeveld, A., Setten, J. van, Gijsberts, C.M., Maitland-van der Zee, A.H., Saely, C.H., Gong, Y., Johnson, J.A., Cooper-DeHoff, R.M., Pepine, C.J., Casu, G., Leiherer, A., Drexel, H., Horne, B.D., Laan, S.W. van der, Marziliano, N., Hazen, S.L., Sinisalo, J., Kahonen, M., Lehtimaki, T., Lang, C.C., Burkhardt, R., Scholz, M., Jukema, J.W., Eriksson, N., Akerblom, A., James, S., Held, C., Hagstrom, E., Spertus, J.A., Algra, A., Faire, U. de, Akesson, A., Asselbergs, F.W., Patel, R.S., Leander, K., HUS Heart and Lung Center, Department of Medicine, Clinicum, University of Helsinki, Pulmonology, Paediatric Pulmonology, APH - Personalized Medicine, ACS - Heart failure & arrhythmias, Tampere University, Department of Clinical Chemistry, Clinical Medicine, and TAYS Heart Centre

Subjects
RISK, ARCHITECTURE, Kardiologi, HYPERTENSION, PGC-1-ALPHA, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], VARIANT, 1184 Genetics, developmental biology, physiology, meta-analysis, PGC-1, cohort studies, PGC1-ALPHA, PPARGC1A, GLY482SER POLYMORPHISM, ARTERY-DISEASE, Cardiac and Cardiovascular Systems, 3111 Biomedicine, PPAR-GAMMA, coronary heart disease, polymorphisms, SNPs
Abstract

Contains fulltext : 283506.pdf (Publisher’s version ) (Open Access) Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.

Published
2022

16. Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data

Author

Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., Patel, R.S., Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., and Patel, R.S.

Abstract

Contains fulltext : 235380.pdf (Publisher’s version ) (Closed access), BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I(2)=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, card

Published
2020

17. Discordance between N-acetyltransferase 2 phenotype and genotype in a population of Hmong subjects

Author

Straka, Robert J., Burkhardt, R. Todd, Lang, Nicholas P., Hadsall, Kelly Z., and Tsai, Michael Y.

Subjects
Hmong (Asian people) -- Health aspects -- Research, Genetic polymorphisms -- Research -- Health aspects, Drugs -- Health aspects, Health, Complications and side effects, Research, Health aspects
Abstract

Polymorphisms of N-acetyltransferase 2 (NAT2) acetylation may influence drug toxicities and efficacy and are associated with a differential susceptibility to select cancers. Acetylation phenotype may have clinical implications. The purposes [...]

Published
2006

18. Sphingosine 1-phosphate (S1P) receptor type 1 signaling induces an anti-atherogenic phenotype in macrophages and attenuates atherosclerosis in LDL-receptor-deficient mice

Author

Potì, F., primary, Scalera, E., additional, Feuerborn, R., additional, Fischer, J., additional, Arndt, L., additional, Varga, G., additional, Pardali, E., additional, Seidl, M., additional, Liebisch, G., additional, Rosenbauer, F., additional, Renne, T., additional, Christoffersen, C., additional, Simoni, M., additional, Burkhardt, R., additional, and Nofer, J.-R., additional

Published
2020
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23. Genetic architecture of subcortical brain structures in 38,854 individuals worldwide

Author

Satizabal, C., Adams, H., Hibar, D., White, C., Knol, M., Stein, J., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G., Smith, A., Bis, J., Jian, X., Luciano, M., Hofer, E., Teumer, A., Van der Lee, S., Yang, J., Yanek, L., Lee, T., Li, S., Hu, Y., Koh, J., Eicher, J., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M., Kim, S., Höhn, D., Armstrong, N., Chen, Q., Holmes, A., Den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A., Jones, H., Pike, G., Stein, D., Stevens, A., Bralten, J., Vernooij, M., Harris, T., Filippi, I., Witte, A., Guadalupe, T., Wittfeld, K., Mosley, T., Becker, J., Doan, N., Hagenaars, S., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Karbalai, N., Arfanakis, K., Becker, D., Ames, D., Goldman, A., Lee, P., Boomsma, D., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M., Kasperaviciute, D., Schmaal, L., Lawrie, S., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G., Shin, J., Ipser, J., Vinke, L., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U., Aribisala, B., Schmidt, H., Strike, L., Cheng, C., Risacher, S., Pütz, B., Fleischman, D., Assareh, A., Mattay, V., Buckner, R., Mecocci, P., Dale, A., Cichon, S., Boks, M., Matarin, M., Penninx, B., Calhoun, V., Chakravarty, M., Marquand, A., Macare, C., Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J., Schork, A., Liewald, D., De Zubicaray, G., Wong, T., Shen, L., Sämann, P., Brodaty, H., Roffman, J., De Geus, E., Tsolaki, M., Erk, S., Van Eijk, K., Cavalleri, G., Van der Wee, N., McIntosh, A., Gollub, R., Bulayeva, K., Bernard, M., Richards, J., Himali, J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L., Valdés Hernández, M., Hansell, N., Van Erp, T., Wolf, C., Kwok, J., Vellas, B., Heinz, A., Olde Loohuis, L., Delanty, N., Ho, B., Ching, C., Shumskaya, E., Singh, B., Hofman, A., Van der Meer, D., Homuth, G., Psaty, B., Bastin, M., Montgomery, G., Foroud, T., Reppermund, S., Hottenga, J., Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C., Van Donkelaar, M., Yang, Q., Hosten, N., Green, R., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H., Lin, H., Jack Jr., C., Schofield, P., Mühleisen, T., Maillard, P., Potkin, S., Wen, W., Fletcher, E., Toga, A., Gruber, O., Huentelman, M., Smith, G., Launer, L., Nyberg, L., Jönsson, E., Crespo-Facorro, B., Koen, N., Greve, D., Uitterlinden, A., Weinberger, D., Steen, V., Fedko, I., Groenewold, N., Niessen, W., Toro, R., Tzourio, C., Longstreth Jr., W., Ikram, M., Smoller, J., Van Tol, M., Sussmann, J., Paus, T., Lemaître, H., Schroeter, M., Mazoyer, B., Andreassen, O., Holsboer, F., Depondt, C., Veltman, D., Turner, J., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I., McMahon, K., Müller-Myhsok, B., Brouwer, R., Soininen, H., Pandolfo, M., Wassink, T., Cheung, J., Wolfers, T., Martinot, J., Zwiers, M., Nauck, M., Melle, I., Martin, N., Kanai, R., Westman, E., Kahn, R., Sisodiya, S., White, T., Saremi, A., Van Bokhoven, H., Brunner, H., Völzke, H., Wright, M., Van 't Ent, D., Nöthen, M., Ophoff, R., Buitelaar, J., Fernández, G., Sachdev, P., Rietschel, M., Van Haren, N., Fisher, S., Beiser, A., Francks, C., Saykin, A., Mather, K., Romanczuk-Seiferth, N., Hartman, C., DeStefano, A., Heslenfeld, D., Weiner, M., Walter, H., Hoekstra, P., Nyquist, P., Franke, B., Bennett, D., Grabe, H., Johnson, A., Chen, C., Van Duijn, C., Lopez, O., Fornage, M., Wardlaw, J., Schmidt, R., DeCarli, C., De Jager, P., Villringer, A., Debette, S., Gudnason, V., Medland, S., Shulman, J., Thompson, P., and Seshadri, S.

Subjects
nervous system
Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019

24. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events A GENIUS-CHD Study of Individual Participant Data

Author

Patel, R.S., Schmidt, A.F., Tragante, V., McCubrey, R.O., Holmes, M.V., Howe, L.J., Direk, K., Akerblom, A., Leander, K., Virani, S.S., Kaminski, K.A., Muehlschlegel, J.D., Dube, M.P., Allayee, H., Almgren, P., Alver, M., Baranova, E.V., Behlouli, H., Boeckx, B., Braund, P.S., Breitling, L.P., Delgado, G., Duarte, N.E., Dufresne, L., Eriksson, N., Foco, L., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Hubacek, J.A., Kleber, M., Kofink, D., Kuukasjarvi, P., Lee, V.V., Leiherer, A., Lenzini, P.A., Levin, D., Lyytikainen, L.P., Martinelli, N., Mons, U., Nelson, C.P., Nikus, K., Pilbrow, A.P., Ploski, R., Sun, Y.V., Tanck, M.W.T., Tang, W.H.W., Trompet, S., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Anselmi, C.V., Vlachopoulou, E., Boerwinkle, E., Briguori, C., Carlquist, J.F., Carruthers, K.F., Casu, G., Deanfield, J., Deloukas, P., Dudbridge, F., Fitzpatrick, N., Gigante, B., James, S., Lokki, M.L., Lotufo, P.A., Marziliano, N., Mordi, I.R., Muhlestein, J.B., Cheh, C.N., Pitha, J., Saely, C.H., Samman-Tahhan, A., Sandesara, P.B., Teren, A., Timmis, A., Werf, F. van de, Wauters, E., Wilde, A.A.M., Ford, I., Stott, D.J., Algra, A., Andreassi, M.G., Ardissino, D., Arsenault, B.J., Ballantyne, C.M., Bergmeijer, T.O., Bezzina, C.R., Body, S.C., Bogaty, P., Borst, G.J. de, Brenner, H., Burkhardt, R., Carpeggiani, C., Condorelli, G., Cooper-DeHoff, R.M., Cresci, S., Faire, U. de, Doughty, R.N., Drexel, H., Engert, J.C., Fox, K.A.A., Girelli, D., Hagstrom, E., Hazen, S.L., Held, C., Hemingway, H., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Jong, P.A. de, Jukema, J.W., Kaczor, M.P., Kahonen, M., Kettner, J., Kiliszek, M., Klungel, O.H., Lagerqvist, B., Lambrechts, D., Laurikka, J.O., Lehtimaki, T., Lindholm, D., Mahmoodi, B.K., Maitland-van der Zee, A.H., McPherson, R., Melander, O., Metspalu, A., Pepinski, W., Olivieri, O., Opolski, G., Palmer, C.N., Pasterkamp, G., Pepine, C.J., Pereira, A.C., Note, L., Quyyumi, A.A., Richards, A.M., Sanak, M., Scholz, M., Siegbahn, A., Sinisalo, J., Smith, J.G., Spertus, J.A., Stewart, A.F.R., Szczeklik, W., Szpakowicz, A., Berg, J.M. ten, Thanassoulis, G., Thieiy, J., Graaf, Y. van der, Visseren, F.L.J., Waltenberger, J., Harst, P. van der, Tardif, J.C., Sattar, N., Lang, C.C., Pare, G., Brophy, J.M., Anderson, J.L., Marz, W., Wallentin, L., Cameron, V.A., Horne, B.D., Samani, N.J., Hingorani, A.D., Asselbergs, F.W., and CARDIo-GRAMPlusC4D Consortium

Subjects
myocardial infarction, risk factor, cardiovascular diseases, chromosome, genetic, variation, secondary prevention
Abstract

BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Published
2019

25. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events

Author

Patel, RS, Schmidt, AF, Tragante, V, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Muehlschlegel, JD, Dubé, M-P, Allayee, H, Almgren, P, Alver, M, Baranova, EV, Behlouli, H, Boeckx, B, Braund, PS, Breitling, LP, Delgado, G, Duarte, NE, Dufresne, L, Eriksson, N, Foco, L, Gijsberts, CM, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Sun, YV, Tanck, MWT, Tang, WHW, Trompet, S, Van Der Laan, SW, Van Setten, J, Vilmundarson, RO, Anselmi, C, Vlachopoulou, E, Boerwinkle, E, Briguori, C, Carlquist, JF, Carruthers, KF, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Fitzpatrick, N, Gigante, B, James, S, Lokki, M-L, Lotufo, PA, Marziliano, N, Mordi, IR, Muhlestein, JB, Newton-Cheh, C, Pitha, J, Saely, CH, Samman-Tahhan, A, Sandesara, PB, Teren, A, Timmis, A, Van De Werf, F, Wauters, E, Wilde, AAM, Ford, I, Stott, DJ, Algra, A, Andreassi, MG, Ardissino, D, Arsenault, BJ, Ballantyne, CM, Bergmeijer, TO, Bezzina, CR, Body, SC, Bogaty, P, De Borst, GJ, Brenner, H, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-Dehoff, RM, Cresci, S, De Faire, U, Doughty, RN, Drexel, H, Engert, JC, Fox, KAA, Girelli, D, Hagström, E, Hazen, SL, Held, C, Hemingway, H, Hoefer, IE, Hovingh, GK, Johnson, JA, De Jong, PA, Jukema, JW, Kaczor, MP, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, OH, Lagerqvist, B, Lambrechts, D, Laurikka, JO, Lehtimäki, T, Lindholm, D, Mahmoodi, BK, Der Zee, AH, McPherson, R, Melander, O, Metspalu, A, Pepinski, W, Olivieri, O, Opolski, G, Palmer, CN, Pasterkamp, G, Pepine, CJ, Pereira, AC, Pilote, L, Quyyumi, AA, Richards, AM, Sanak, M, Scholz, M, Siegbahn, A, Sinisalo, J, Smith, JG, Spertus, JA, Stewart, AFR, Szczeklik, W, Szpakowicz, A, Berg, JM, Thanassoulis, G, Thiery, J, Van Der Graaf, Y, Visseren, FLJ, Waltenberger, J, Van Der Harst, P, Tardif, J-C, Sattar, N, Lang, CC, Paré, G, Brophy, JM, Anderson, JL, März, W, Wallentin, L, Cameron, VA, Horne, BD, Samani, NJ, Hingorani, AD, and Asselbergs, FW

Subjects
Male, Myocardial Infarction, genetic risk factor, Coronary Artery Disease, Middle Aged, Article, chromosome 9p21, Gene Frequency, Risk Factors, Case-Control Studies, Odds Ratio, Humans, Female, Genetic Predisposition to Disease, cardiovascular diseases, Chromosomes, Human, Pair 9, secondary prevention
Abstract

Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Published
2019

26. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

SATIZABAL, C. L., ADAMS, H. H. H., HIBAR, D. P., WHITE, C. C., KNOL, M. J., STEIN, J. L., Scholz, M., Sargurupremraj, Muralidharan, JAHANSHAD, N., ROSHCHUPKIN, G. V., SMITH, A. V., BIS, J. C., JIAN, X., LUCIANO, M., Hofer, E., TEUMER, A., VAN DER LEE, S. J., Yang, J., YANEK, L. R., LEE, T. V., Li, S., Hu, Y., KOH, J. Y., EICHER, J. D., DESRIVIERES, S., ARIAS-VASQUEZ, A., Chauhan, G., ATHANASIU, L., RENTERIA, M. E., Kim, S., HOEHN, D., ARMSTRONG, N. J., Chen, Q., HOLMES, A. J., DEN BRABER, A., KLOSZEWSKA, I., Andersson, M., ESPESETH, T., Grimm, O., ABRAMOVIC, L., ALHUSAINI, S., MILANESCHI, Y., PAPMEYER, M., AXELSSON, T., Ehrlich, S., ROIZ-SANTIANEZ, R., KRAEMER, B., HABERG, A. K., JONES, H. J., Pike, G. B., STEIN, D. J., Stevens, A., BRALTEN, J., VERNOOIJ, M. W., HARRIS, T. B., FILIPPI, I., WITTE, A. V., Guadalupe, T., WITTFELD, K., MOSLEY, T. H., BECKER, J. T., DOAN, N. T., HAGENAARS, S. P., SABA, Y., CUELLAR-PARTIDA, G., Amin, N., HILAL, S., NHO, K., MIRZA-SCHREIBER, N., ARFANAKIS, K., BECKER, D. M., Ames, D., GOLDMAN, A. L., LEE, P. H., Boomsma, D. I., LOVESTONE, S., GIDDALURU, S., LE HELLARD, S., Mattheisen, M., BOHLKEN, M. M., KASPERAVICIUTE, D., SCHMAAL, L., LAWRIE, S. M., Agartz, I., Walton, E., TORDESILLAS-GUTIERREZ, D., DAVIES, G. E., Shin, J., IPSER, J. C., VINKE, L. N., HOOGMAN, M., Jia, T., BURKHARDT, R., Klein, M., Crivello, Fabrice, JANOWITZ, D., CARMICHAEL, O., HAUKVIK, U. K., ARIBISALA, B. S., Schmidt, H., STRIKE, L. T., CHENG, C. Y., RISACHER, S. L., PUTZ, B., FLEISCHMAN, D. A., ASSAREH, A. A., MATTAY, V. S., BUCKNER, R. L., MECOCCI, P., DALE, A. M., Cichon, S., BOKS, M. P., MATARIN, M., PENNINX, Bwjh, CALHOUN, V. D., CHAKRAVARTY, M. M., MARQUAND, A. F., MACARE, C., KHARABIAN MASOULEH, S., OOSTERLAAN, J., Amouyel, P., HEGENSCHEID, K., ROTTER, J. I., SCHORK, A. J., LIEWALD, D. C. M., DE ZUBICARAY, G. I., WONG, T. Y., Shen, L., SAMANN, P. G., BRODATY, H., ROFFMAN, J. L., DE GEUS, E. J. C., TSOLAKI, M., ERK, S., VAN EIJK, K. R., CAVALLERI, G. L., VAN DER WEE, N. J. A., MCINTOSH, A. M., GOLLUB, R. L., BULAYEVA, K. B., Bernard, M., RICHARDS, J. S., HIMALI, J. J., Loeffler, M., ROMMELSE, N., Hoffmann, W., WESTLYE, L. T., VALDES HERNANDEZ, M. C., HANSELL, N. K., VAN ERP, T. G. M., Wolf, C., KWOK, J. B. J., Vellas, B., Heinz, A., OLDE LOOHUIS, L. M., DELANTY, N., HO, B. C., CHING, C. R. K., SHUMSKAYA, E., Singh, B., Hofman, A., VAN DER MEER, D., Homuth, G., PSATY, B. M., BASTIN, M. E., MONTGOMERY, G. W., FOROUD, T. M., REPPERMUND, S., HOTTENGA, J. J., Simmons, A., Meyer-Lindenberg, A., Cahn, W., WHELAN, C. D., VAN DONKELAAR, M. M. J., Yang, Q., HOSTEN, N., GREEN, R. C., THALAMUTHU, A., MOHNKE, S., HULSHOFF POL, H. E., Lin, H., JACK, C. R., Jr., SCHOFIELD, P. R., MUHLEISEN, T. W., MAILLARD, P., POTKIN, S. G., Wen, W., FLETCHER, E., TOGA, A. W., Gruber, O., HUENTELMAN, M., DAVEY SMITH, G., LAUNER, L. J., Nyberg, L., JONSSON, E. G., CRESPO-FACORRO, B., KOEN, N., GREVE, D. N., UITTERLINDEN, A. G., WEINBERGER, D. R., STEEN, V. M., FEDKO, I. O., GROENEWOLD, N. A., Niessen, W. J., TORO, R., Tzourio, Christophe, LONGSTRETH, W. T., Jr., SMOLLER, J. W., VAN TOL, M. J., SUSSMANN, J. E., PAUS, T., Lemaitre, H., SCHROETER, M. L., Mazoyer, B., ANDREASSEN, O. A., Holsboer, F., DEPONDT, C., VELTMAN, D. J., Turner, J. A., PAUSOVA, Z., Schumann, G., Van Rooij, D., Djurovic, S., DEARY, I. J., MCMAHON, K. L., MULLER-MYHSOK, B., BROUWER, R. M., Soininen, H., Pandolfo, M., WASSINK, T. H., CHEUNG, J. W., WOLFERS, T., MARTINOT, J. L., ZWIERS, M. P., Nauck, M., Melle, I., Martin, N. G., Kanai, R., WESTMAN, E., KAHN, R. S., Sisodiya, S. M., White, T., SAREMI, A., van Bokhoven, H., Brunner, H. G., VOLZKE, H., WRIGHT, M. J., VAN 'T ENT, D., NOTHEN, M. M., OPHOFF, R. A., BUITELAAR, J. K., Fernandez, G., SACHDEV, P. S., Rietschel, M., VAN HAREN, N. E. M., Fisher, S. E., BEISER, A. S., Francks, C., SAYKIN, A. J., MATHER, K. A., ROMANCZUK-SEIFERTH, N., HARTMAN, C. A., DeStefano, A. L., HESLENFELD, D. J., WEINER, M. W., Walter, H., HOEKSTRA, P. J., NYQUIST, P. A., Franke, B., BENNETT, D. A., Grabe, H. J., JOHNSON, A. D., Chen, C., VAN DUIJN, C. M., LOPEZ, O. L., FORNAGE, M., WARDLAW, J. M., Schmidt, R., DeCarli, C., DE JAGER, P. L., VILLRINGER, A., Debette, Stephanie, GUDNASON, V., Medland, S. E., SHULMAN, J. M., THOMPSON, P. M., SESHADRI, S., IKRAM, M. K., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
nervous system, VINTAGE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTHY
Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019
Full Text
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27. Human brain arousal in the resting state: A genome-wide association study

Author

Jawinski, P., Kirsten, H., Sander, C., Spada, J., Ulke, C., Huang, J., Burkhardt, R., Scholz, M., Hensch, T., Hegerl, U., and Publica

Abstract

Arousal affects cognition, emotion, and behavior and has been implicated in the etiology of psychiatric disorders. Although environmental conditions substantially contribute to the level of arousal, stable interindividual characteristics are well-established and a genetic basis has been suggested. Here we investigated the molecular genetics of brain arousal in the resting state by conducting a genome-wide association study (GWAS). We selected N = 1877 participants from the population-based LIFE-Adult cohort. Participants underwent a 20-min eyes-closed resting state EEG, which was analyzed using the computerized VIGALL 2.1 (Vigilance Algorithm Leipzig). At the SNP-level, GWAS analyses revealed no genome-wide significant locus (p

Published
2019

30. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

Satizabal, C.L., Adams, H.H.H., Hibar, D.P., White, C.C., Knol, M.J., Stein, J.L., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G.V., Smith, A.V., Bis, J.C., Jian, X., Luciano, M., Hofer, E., Teumer, A., van der Lee, S.J., Yang, J., Yanek, L.R., Lee, T.V., Li, S., Hu, Y., Koh, J.Y., Eicher, J.D., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M.E., Kim, S., Hoehn, D., Armstrong, N.J., Chen, Q., Holmes, A.J., den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A.K., Jones, H.J., Pike, G.B., Stein, D.J., Stevens, A., Bralten, J., Vernooij, M.W., Harris, T.B., Filippi, I., Witte, A.V., Guadalupe, T., Wittfeld, K., Mosley, T.H., Becker, J.T., Doan, N.T., Hagenaars, S.P., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Mirza-Schreiber, N., Arfanakis, K., Becker, D.M., Ames, D., Goldman, A.L., Lee, P.H., Boomsma, D.I., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M.M., Kasperaviciute, D., Schmaal, L., Lawrie, S.M., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G.E., Shin, J., Ipser, J.C., Vinke, L.N., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U.K., Aribisala, B.S., Schmidt, H., Strike, L.T., Cheng, C-Y, Risacher, S.L., Pütz, B., Fleischman, D.A., Assareh, A.A., Mattay, V.S., Buckner, R.L., Mecocci, P., Dale, A.M., Cichon, S., Boks, M.P., Matarin, M., Penninx, B.W.J.H., Calhoun, V.D., Chakravarty, M.M., Marquand, A.F., Macare, C., Kharabian Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J.I., Schork, A.J., Liewald, D.C.M., de Zubicaray, G.I., Wong, T.Y., Shen, L., Sämann, P.G., Brodaty, H., Roffman, J.L., de Geus, E.J.C., Tsolaki, M., Erk, S., van Eijk, K.R., Cavalleri, G.L., van der Wee, N.J.A., McIntosh, A.M., Gollub, R.L., Bulayeva, K.B., Bernard, M., Richards, J.S., Himali, J.J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L.T., Valdés Hernández, M.C., Hansell, N.K., Van Erp, T.G.M., Wolf, C., Kwok, J.B.J., Vellas, B., Heinz, A., Olde Loohuis, L.M., Delanty, N., Ho, B-C., Ching, C.R.K., Shumskaya, E., Singh, B., Hofman, A., van der Meer, D., Homuth, G., Psaty, B.M., Bastin, M.E., Montgomery, G.W., Foroud, T.M., Reppermund, S., Hottenga, J-J, Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C.D., van Donkelaar, M.M.J., Yang, Q., Hosten, N., Green, R.C., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H.E., Lin, H., Jack, C.R., Schofield, P.R., Mühleisen, T.W., Maillard, P., Potkin, S.G., Wen, W., Fletcher, E., Toga, A.W., Gruber, O., Huentelman, M., Davey Smith, G., Launer, L.J., Nyberg, L., Jönsson, E.G., Crespo-Facorro, B., Koen, N., Greve, D.N., Uitterlinden, A.G., Weinberger, D.R., Steen, V.M., Fedko, I.O., Groenewold, N.A., Niessen, W.J., Toro, R., Tzourio, C., Longstreth, W.T., Ikram, M.K., Smoller, J.W., van Tol, M-J, Sussmann, J.E., Paus, T., Lemaitre, H., Schroeter, M.L., Mazoyer, B., Andreassen, O.A., Holsboer, F., Depondt, C., Veltman, D.J., Turner, J.A., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I.J., McMahon, K.L., Müller-Myhsok, B., Brouwer, R.M., Soininen, H., Pandolfo, M., Wassink, T.H., Cheung, J.W., Wolfers, T., Martinot, J-L, Zwiers, M.P., Nauck, M., Melle, I., Martin, N.G., Kanai, R., Westman, E., Kahn, R.S., Sisodiya, S.M., White, T., Saremi, A., van Bokhoven, H., Brunner, H.G., Völzke, H., Wright, M.J., van ‘t Ent, D., Nöthen, M.M., Ophoff, R.A., Buitelaar, J.K., Fernández, G., Sachdev, P.S., Rietschel, M., van Haren, N.E.M., Fisher, S.E., Beiser, A.S., Francks, C., Saykin, A.J., Mather, K.A., Romanczuk-Seiferth, N., Hartman, C.A., DeStefano, A.L., Heslenfeld, D.J., Weiner, M.W., Walter, H., Hoekstra, P.J., Nyquist, P.A., Franke, B., Bennett, D.A., Grabe, H.J., Johnson, A.D., Chen, C., van Duijn, C.M., Lopez, O.L., Fornage, M., Wardlaw, J.M., Schmidt, R., DeCarli, C., De Jager, P.L., Villringer, A., Debette, S., Gudnason, V., Medland, S.E., Shulman, J.M., Thompson, P.M., Seshadri, S., Ikram, M.A., Satizabal, C.L., Adams, H.H.H., Hibar, D.P., White, C.C., Knol, M.J., Stein, J.L., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G.V., Smith, A.V., Bis, J.C., Jian, X., Luciano, M., Hofer, E., Teumer, A., van der Lee, S.J., Yang, J., Yanek, L.R., Lee, T.V., Li, S., Hu, Y., Koh, J.Y., Eicher, J.D., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M.E., Kim, S., Hoehn, D., Armstrong, N.J., Chen, Q., Holmes, A.J., den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A.K., Jones, H.J., Pike, G.B., Stein, D.J., Stevens, A., Bralten, J., Vernooij, M.W., Harris, T.B., Filippi, I., Witte, A.V., Guadalupe, T., Wittfeld, K., Mosley, T.H., Becker, J.T., Doan, N.T., Hagenaars, S.P., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Mirza-Schreiber, N., Arfanakis, K., Becker, D.M., Ames, D., Goldman, A.L., Lee, P.H., Boomsma, D.I., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M.M., Kasperaviciute, D., Schmaal, L., Lawrie, S.M., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G.E., Shin, J., Ipser, J.C., Vinke, L.N., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U.K., Aribisala, B.S., Schmidt, H., Strike, L.T., Cheng, C-Y, Risacher, S.L., Pütz, B., Fleischman, D.A., Assareh, A.A., Mattay, V.S., Buckner, R.L., Mecocci, P., Dale, A.M., Cichon, S., Boks, M.P., Matarin, M., Penninx, B.W.J.H., Calhoun, V.D., Chakravarty, M.M., Marquand, A.F., Macare, C., Kharabian Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J.I., Schork, A.J., Liewald, D.C.M., de Zubicaray, G.I., Wong, T.Y., Shen, L., Sämann, P.G., Brodaty, H., Roffman, J.L., de Geus, E.J.C., Tsolaki, M., Erk, S., van Eijk, K.R., Cavalleri, G.L., van der Wee, N.J.A., McIntosh, A.M., Gollub, R.L., Bulayeva, K.B., Bernard, M., Richards, J.S., Himali, J.J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L.T., Valdés Hernández, M.C., Hansell, N.K., Van Erp, T.G.M., Wolf, C., Kwok, J.B.J., Vellas, B., Heinz, A., Olde Loohuis, L.M., Delanty, N., Ho, B-C., Ching, C.R.K., Shumskaya, E., Singh, B., Hofman, A., van der Meer, D., Homuth, G., Psaty, B.M., Bastin, M.E., Montgomery, G.W., Foroud, T.M., Reppermund, S., Hottenga, J-J, Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C.D., van Donkelaar, M.M.J., Yang, Q., Hosten, N., Green, R.C., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H.E., Lin, H., Jack, C.R., Schofield, P.R., Mühleisen, T.W., Maillard, P., Potkin, S.G., Wen, W., Fletcher, E., Toga, A.W., Gruber, O., Huentelman, M., Davey Smith, G., Launer, L.J., Nyberg, L., Jönsson, E.G., Crespo-Facorro, B., Koen, N., Greve, D.N., Uitterlinden, A.G., Weinberger, D.R., Steen, V.M., Fedko, I.O., Groenewold, N.A., Niessen, W.J., Toro, R., Tzourio, C., Longstreth, W.T., Ikram, M.K., Smoller, J.W., van Tol, M-J, Sussmann, J.E., Paus, T., Lemaitre, H., Schroeter, M.L., Mazoyer, B., Andreassen, O.A., Holsboer, F., Depondt, C., Veltman, D.J., Turner, J.A., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I.J., McMahon, K.L., Müller-Myhsok, B., Brouwer, R.M., Soininen, H., Pandolfo, M., Wassink, T.H., Cheung, J.W., Wolfers, T., Martinot, J-L, Zwiers, M.P., Nauck, M., Melle, I., Martin, N.G., Kanai, R., Westman, E., Kahn, R.S., Sisodiya, S.M., White, T., Saremi, A., van Bokhoven, H., Brunner, H.G., Völzke, H., Wright, M.J., van ‘t Ent, D., Nöthen, M.M., Ophoff, R.A., Buitelaar, J.K., Fernández, G., Sachdev, P.S., Rietschel, M., van Haren, N.E.M., Fisher, S.E., Beiser, A.S., Francks, C., Saykin, A.J., Mather, K.A., Romanczuk-Seiferth, N., Hartman, C.A., DeStefano, A.L., Heslenfeld, D.J., Weiner, M.W., Walter, H., Hoekstra, P.J., Nyquist, P.A., Franke, B., Bennett, D.A., Grabe, H.J., Johnson, A.D., Chen, C., van Duijn, C.M., Lopez, O.L., Fornage, M., Wardlaw, J.M., Schmidt, R., DeCarli, C., De Jager, P.L., Villringer, A., Debette, S., Gudnason, V., Medland, S.E., Shulman, J.M., Thompson, P.M., Seshadri, S., and Ikram, M.A.

Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019

31. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Author

Teumer, A. (Alexander), Li, Y. (Yong), Ghasemi, S. (Sahar), Prins, B.P. (Bram Peter), Wuttke, M. (Matthias), Hermle, T. (Tobias), Giri, A. (Ayush), Sieber, K.B. (Karsten B.), Qiu, C. (Chengxiang), Kirsten, H. (Holger), Tin, A. (Adrienne), Chu, A.Y. (Audrey Y), Bansal, N. (Nisha), Feitosa, M.F. (Mary Furlan), Wang, L. (Lihua), Chai, J.-F. (Jin-Fang), Cocca, M. (Massimiliano), Fuchsberger, C. (Christian), Gorski, M. (Mathias), Hoppmann, A. (Anselm), Horn, K. (Katrin), Li, M. (Man), Marten, J. (Jonathan), Noce, D. (Damia), Nutile, T. (Teresa), Sedaghat, S. (Sanaz), Sveinbjornsson, G. (Gardar), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Xu, Y. (Yizhe), Yu, Z. (Zhi), Gerstner, L. (Lea), Ärnlöv, J. (Johan), Bakker, S.J.L. (Stephan), Baptista, D. (Daniela), Biggs, M.L. (M.), Boerwinkle, E.A. (Eric), Brenner, H. (Hermann), Burkhardt, R. (Ralph), Carroll, R.J. (Robert J.), Chee, M.-L. (Miao-Li), Chee, M.-L. (Miao-Ling), Chen, M. (Mengmeng), Cheng, C.-Y. (Ching-Yu), Cook, J.P. (James P.), Coresh, J. (Josef), Corre, T. (Tanguy), Danesh, J. (John), de Borst, M.H. (Martin H.), Grandi, A. (Alessandro) de, Mutsert, R. (Reneé) de, de Vries, A.P.J. (Aiko P J), Degenhardt, F. (Frauke), Dittrich, K. (Katalin), Divers, J. (Jasmin), Eckardt, K.-U. (Kai-Uwe), Ehret, G.B. (Georg), Endlich, K. (Karlhans), Felix, J.F. (Janine), Franco, O.H. (Oscar), Franke, A. (Andre), Freedman, B.I. (Barry), Freitag-Wolf, S. (Sandra), Gansevoort, R.T. (Ron), Giedraitis, V. (Vilmantas), Gögele, M. (Martin), Grundner-Culemann, F. (Franziska), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hamet, P. (Pavel), Harris, T.B. (Tamara), Hicks, A.A. (Andrew A.), Holm, H. (Hilma), Foo, V.H.X. (Valencia Hui Xian), Hwang, S.-J. (Shih-Jen), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Jaddoe, V.W.V. (Vincent), Jakobsdottir, M. (Margret), Josyula, N.S. (Navya Shilpa), Jung, B. (Bettina), Kähönen, M. (Mika), Khor, C.C., Kieß, W. (Wieland), Koenig, W. (Wolfgang), Körner, A. (Antje), Kovacs, P. (Peter), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kronenberg, F. (Florian), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Lee, J.J.-M. (Jeannette Jen-Mai), Lehtimäki, T. (Terho), Lieb, W. (Wolfgang), Lim, S.-C. (Su-Chi), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, J. (Jianjun), Loeffler, M. (Markus), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Maranville, J.C. (Joseph C.), Mascalzoni, D. (Deborah), McMullen, B. (Barbara), Meisinger, C. (Christa), Meitinger, T. (Thomas), Miliku, K. (Kozeta), Mook-Kanamori, D.O. (Dennis O.), Müller-Nurasyid, M. (Martina), Mychaleckyj, J.C. (Josyf), Nauck, M. (Matthias), Nikus, K. (Kjell), Ning, B. (Boting), Noordam, R. (Raymond), Connell, J.O. (Jeffrey O'), Olafsson, I. (Isleifur), Palmer, N.D. (Nicholette), Peters, A. (Annette), Podgornaia, A.I. (Anna I.), Ponte, B. (Belen), Poulain, T. (Tanja), Pramstaller, P.P. (Peter Paul), Rabelink, T. (Ton), Raffield, L.M. (Laura M.), Reilly, D.F. (Dermot F.), Rettig, R. (Rainer), Rheinberger, M. (Myriam), Rice, K.M. (Kenneth), Rivadeneira, F. (Fernando), Runz, H. (Heiko), Ryan, K.A. (Kathleen A.), Sabanayagam, C. (Charumathi), Saum, K.-U. (Kai-Uwe), Schöttker, B. (Ben), Shaffer, C.M. (Christian M.), Shi, Y. (Yuan), Smith, A.V. (Albert), Strauch, K. (Konstantin), Stumvoll, M. (Michael), Sun, B.B. (Benjamin B.), Szymczak, S. (Silke), Tai, E.-S. (E-Shyong), Tan, N.Y.Q. (Nicholas Y Q), Taylor, K.D. (Kent), Teren, A. (Andrej), Tham, Y.-C. (Yih-Chung), Thiery, J. (Joachim), Thio, C.H.L. (Chris H L), Thomsen, H. (Hauke), Thorsteinsdottir, U. (Unnur), Tönjes, A. (Anke), Tremblay, J. (Johanne), Uitterlinden, A.G. (André), Harst, P. (Pim) van der, Verweij, N. (Niek), Vogelezang, S., Völker, U. (Uwe), Waldenberger, M. (Melanie), Wang, C. (Chunliang), Wilson, O.D. (Otis D.), Wong, C. (Charlene), Wong, T.-Y. (Tien-Yin), Yang, Q. (Qiong), Yasuda, M. (Masayuki), Akilesh, S. (Shreeram), Bochud, M. (Murielle), Böger, C.A. (Carsten), Devuyst, O. (Olivier), Edwards, T.L. (Todd L.), Ho, K. (Kevin), Morris, A.P. (Andrew), Parsa, A. (Afshin), Pendergrass, S.A. (Sarah), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome I.), Zwart, J-A. (John-Anker), Wilson, J.F. (James), Susztak, K. (Katalin), Snieder, H. (Harold), Heid, I.M. (Iris), Scholz, M. (Markus), Butterworth, A.S. (Adam S.), Hung, A.M. (Adriana M.), Penninx, B.W.J.H., Köttgen, A. (Anna), Teumer, A. (Alexander), Li, Y. (Yong), Ghasemi, S. (Sahar), Prins, B.P. (Bram Peter), Wuttke, M. (Matthias), Hermle, T. (Tobias), Giri, A. (Ayush), Sieber, K.B. (Karsten B.), Qiu, C. (Chengxiang), Kirsten, H. (Holger), Tin, A. (Adrienne), Chu, A.Y. (Audrey Y), Bansal, N. (Nisha), Feitosa, M.F. (Mary Furlan), Wang, L. (Lihua), Chai, J.-F. (Jin-Fang), Cocca, M. (Massimiliano), Fuchsberger, C. (Christian), Gorski, M. (Mathias), Hoppmann, A. (Anselm), Horn, K. (Katrin), Li, M. (Man), Marten, J. (Jonathan), Noce, D. (Damia), Nutile, T. (Teresa), Sedaghat, S. (Sanaz), Sveinbjornsson, G. (Gardar), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Xu, Y. (Yizhe), Yu, Z. (Zhi), Gerstner, L. (Lea), Ärnlöv, J. (Johan), Bakker, S.J.L. (Stephan), Baptista, D. (Daniela), Biggs, M.L. (M.), Boerwinkle, E.A. (Eric), Brenner, H. (Hermann), Burkhardt, R. (Ralph), Carroll, R.J. (Robert J.), Chee, M.-L. (Miao-Li), Chee, M.-L. (Miao-Ling), Chen, M. (Mengmeng), Cheng, C.-Y. (Ching-Yu), Cook, J.P. (James P.), Coresh, J. (Josef), Corre, T. (Tanguy), Danesh, J. (John), de Borst, M.H. (Martin H.), Grandi, A. (Alessandro) de, Mutsert, R. (Reneé) de, de Vries, A.P.J. (Aiko P J), Degenhardt, F. (Frauke), Dittrich, K. (Katalin), Divers, J. (Jasmin), Eckardt, K.-U. (Kai-Uwe), Ehret, G.B. (Georg), Endlich, K. (Karlhans), Felix, J.F. (Janine), Franco, O.H. (Oscar), Franke, A. (Andre), Freedman, B.I. (Barry), Freitag-Wolf, S. (Sandra), Gansevoort, R.T. (Ron), Giedraitis, V. (Vilmantas), Gögele, M. (Martin), Grundner-Culemann, F. (Franziska), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hamet, P. (Pavel), Harris, T.B. (Tamara), Hicks, A.A. (Andrew A.), Holm, H. (Hilma), Foo, V.H.X. (Valencia Hui Xian), Hwang, S.-J. (Shih-Jen), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Jaddoe, V.W.V. (Vincent), Jakobsdottir, M. (Margret), Josyula, N.S. (Navya Shilpa), Jung, B. (Bettina), Kähönen, M. (Mika), Khor, C.C., Kieß, W. (Wieland), Koenig, W. (Wolfgang), Körner, A. (Antje), Kovacs, P. (Peter), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kronenberg, F. (Florian), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Lee, J.J.-M. (Jeannette Jen-Mai), Lehtimäki, T. (Terho), Lieb, W. (Wolfgang), Lim, S.-C. (Su-Chi), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, J. (Jianjun), Loeffler, M. (Markus), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Maranville, J.C. (Joseph C.), Mascalzoni, D. (Deborah), McMullen, B. (Barbara), Meisinger, C. (Christa), Meitinger, T. (Thomas), Miliku, K. (Kozeta), Mook-Kanamori, D.O. (Dennis O.), Müller-Nurasyid, M. (Martina), Mychaleckyj, J.C. (Josyf), Nauck, M. (Matthias), Nikus, K. (Kjell), Ning, B. (Boting), Noordam, R. (Raymond), Connell, J.O. (Jeffrey O'), Olafsson, I. (Isleifur), Palmer, N.D. (Nicholette), Peters, A. (Annette), Podgornaia, A.I. (Anna I.), Ponte, B. (Belen), Poulain, T. (Tanja), Pramstaller, P.P. (Peter Paul), Rabelink, T. (Ton), Raffield, L.M. (Laura M.), Reilly, D.F. (Dermot F.), Rettig, R. (Rainer), Rheinberger, M. (Myriam), Rice, K.M. (Kenneth), Rivadeneira, F. (Fernando), Runz, H. (Heiko), Ryan, K.A. (Kathleen A.), Sabanayagam, C. (Charumathi), Saum, K.-U. (Kai-Uwe), Schöttker, B. (Ben), Shaffer, C.M. (Christian M.), Shi, Y. (Yuan), Smith, A.V. (Albert), Strauch, K. (Konstantin), Stumvoll, M. (Michael), Sun, B.B. (Benjamin B.), Szymczak, S. (Silke), Tai, E.-S. (E-Shyong), Tan, N.Y.Q. (Nicholas Y Q), Taylor, K.D. (Kent), Teren, A. (Andrej), Tham, Y.-C. (Yih-Chung), Thiery, J. (Joachim), Thio, C.H.L. (Chris H L), Thomsen, H. (Hauke), Thorsteinsdottir, U. (Unnur), Tönjes, A. (Anke), Tremblay, J. (Johanne), Uitterlinden, A.G. (André), Harst, P. (Pim) van der, Verweij, N. (Niek), Vogelezang, S., Völker, U. (Uwe), Waldenberger, M. (Melanie), Wang, C. (Chunliang), Wilson, O.D. (Otis D.), Wong, C. (Charlene), Wong, T.-Y. (Tien-Yin), Yang, Q. (Qiong), Yasuda, M. (Masayuki), Akilesh, S. (Shreeram), Bochud, M. (Murielle), Böger, C.A. (Carsten), Devuyst, O. (Olivier), Edwards, T.L. (Todd L.), Ho, K. (Kevin), Morris, A.P. (Andrew), Parsa, A. (Afshin), Pendergrass, S.A. (Sarah), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome I.), Zwart, J-A. (John-Anker), Wilson, J.F. (James), Susztak, K. (Katalin), Snieder, H. (Harold), Heid, I.M. (Iris), Scholz, M. (Markus), Butterworth, A.S. (Adam S.), Hung, A.M. (Adriana M.), Penninx, B.W.J.H., and Köttgen, A. (Anna)

Abstract

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

Published
2019
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32. Subsequent Event Risk in Individuals With Established Coronary Heart Disease

Author

Patel, R.S. (Riyaz), Tragante, V. (Vinicius), Schmidt, A.F. (Amand), McCubrey, R.O. (Raymond O.), Holmes, M.V. (Michael), Howe, L.J. (Laurence J.), Direk, K. (Kenan), Åkerblom, A. (Axel), Leander, K. (Karin), Virani, S.S. (Salim), Kaminski, K.A. (Karol A.), Muehlschlegel, J.D. (Jochen), Allayee, H. (Hooman), Almgren, P. (Peter), Alver, M. (Maris), Baranova, E.V. (Ekaterina V.), Behloui, H. (Hassan), Boeckx, B. (Bram), Braund, P.S. (Peter), Breitling, L.P. (Lutz), Delgado, G., Duarte, N.E. (Nubia E.), Dubé, G.P. (Gregory), Dufresne, L. (Line), Eriksson, N. (Niclas), Foco, L. (Luisa), Scholz, M. (Markus), Gijsberts, C.M. (Crystel M.), Glinge, C. (Charlotte), Gong, Y. (Yan), Hartiala, J. (Jaana), Heydarpour, M. (Mahyar), Hubacek, J.A. (Jaroslav A.), Kleber, M.E. (Marcus), Kofink, D. (Daniel), Kotti, S. (Salma), Kuukasjärvi, P. (Pekka), Lee, V.-V. (Vei-Vei), Leiherer, A. (Andreas), Lenzini, P.A. (Petra A.), Levin, D. (Daniel), Lyytikäinen, L.-P. (Leo-Pekka), Martinelli, N. (Nicola), Mons, U. (Ute), Nelson, C.P. (Christopher P.), Nikus, K. (Kjell), Pilbrow, A.P. (Anna P.), Ploski, R. (Rafal), Sun, Y.V. (Yan V.), Tanck, M.W.T. (Michael), Tang, W. (W.), Trompet, S. (Stella), van der Laan, S.W. (Sander W.), Setten, J. (Jessica) van, Vilmundarson, R.O. (Ragnar O.), Viviani Anselmi, C. (Chiara), Vlachopoulou, E. (Efthymia), Al Ali, L. (Lawien), Boerwinkle, E.A. (Eric), Briguori, C. (Carlo), Carlquist, J.F. (John), Carruthers, K.F. (Kathryn), Casu, G. (Gavino), Deanfield, J. (John), Deloukas, P. (Panos), Dudbridge, F. (Frank), Engstrøm, T. (Thomas), Fitzpatrick, N. (Natalie), Fox, K.M. (Kim), Gigante, B. (Bruna), James, S.K. (Stefan), Lokki, M.-L. (Marja-Liisa), Lotufo, P.A. (Paulo A.), Marziliano, N. (Nicola), Mordi, I.R. (Ify R.), Muhlestein, J.B. (Joseph), Newton-Cheh, C. (Christopher), Pitha, J. (Jan), Saely, C.H. (Christoph H.), Samman-Tahhan, A. (Ayman), Sandesara, P.B. (Pratik B.), Teren, A. (Andrej), Timmis, A. (Adam), Van de Werf, F. (Frans), Wilde, A.A.M. (Arthur), Ford, I. (Ian), Stott, D.J. (David. J.), Algra, A. (Ale), Andreassi, M.G. (Maria G.), Ardissino, D. (Diego), Arsenault, B.J. (Benoit J.), Ballantyne, C. (Christie), Bergmeijer, T.O. (Thomas O.), Bezzina, C.R. (Connie R.), Body, S.C. (Simon C.), Boersma, E.H. (Eric H.), Bogaty, P. (Peter), Bots, M.L. (Michiel), Brenner, H. (Hermann), Brugts, J.J. (Jasper), Burkhardt, R. (Ralph), Carpeggiani, C. (Clara), Condorelli, G. (Gianluigi), Cooper-Dehoff, R.M. (Rhonda), Cresci, S. (Sharon), Danchin, N. (Nicolas), Faire, U. (Ulf) de, Doughty, R.N. (Robert N.), Drexel, H. (Heinz), Engert, J.C. (James C.), Fox, K.A.A. (Keith), Girelli, D. (Domenico), Grobbee, D.E. (Diederick E.), Hagström, E. (Emil), Hazen, S.L. (Stanley), Held, C. (Claes), Hemingway, H., Hoefer, I.E. (Imo), Hovingh, G.K. (G Kees), Jabbari, R. (Reza), Johnson, J.A. (Jennifer ), Jukema, J.W. (Jan Wouter), Kaczor, M.P. (Marcin P.), Kähönen, M. (Mika), Kettner, J. (Jiri), Kiliszek, M. (Marek), Klungel, O.H. (Olaf), Lagerqvist, B. (Bo), Lambrechts, D. (Diether), Laurikka, J.O. (Jari O.), Lehtimäki, T. (Terho), Lindholm, D. (Daniel), Mahmoodi, B.K. (Bakhtawar K.), Maitland-van der Zee, A-H. (Anke-Hilse), McPherson, R. (Ruth), Melander, O. (Olle), Metspalu, A. (Andres), Niemcunowicz-Janica, A. (Anna), Olivieri, O. (Oliviero), Opolski, G. (Grzegorz), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Pepine, C.J. (Carl), Pereira, A. (A.), Pilote, L. (Louise), Erdmann, J. (Jeanette), Richards, A.M. (A Mark), Sanak, M. (Marek), Siegbahn, A. (Agneta), Simon, T. (Tabassome), Sinisalo, J. (Juha), Smith, J.G. (J Gustav), Schwartz, S.M. (Stephen), Stender, S. (Steen), Stewart, A.F. (Alexandre F.), Szczeklik, W. (Wojciech), Szpakowicz, A. (Anna), Tardif, J.-C. (Jean-Claude), Berg, J.M. (Jurrien) ten, Tfelt-Hansen, J. (Jacob), Thanassoulis, G. (George), Thiery, J.P. (Joachim), Torp-Pedersen, C. (Christian Tobias), Graaf, Y. (Yolanda) van der, Visseren, F.L.J. (Frank), Waltenberger, J. (Johannes), Weeke, P.E. (Peter E.), Harst, P. (Pim) van der, Lang, C.C. (Chim C.), Sattar, N. (Naveed), Cameron, V.A. (Vicky A.), Anderson, J.L. (Jeffrey), Brophy, J.M. (James M.), Pare, G. (Guillame), Horne, B.D. (Benjamin), Ye, S. (Shu), Wallentin, L. (Lars), Wauters, E. (Els), Samani, N.J. (Nilesh), Hingorani, A. (Aroon), Asselbergs, F.W. (Folkert), Patel, R.S. (Riyaz), Tragante, V. (Vinicius), Schmidt, A.F. (Amand), McCubrey, R.O. (Raymond O.), Holmes, M.V. (Michael), Howe, L.J. (Laurence J.), Direk, K. (Kenan), Åkerblom, A. (Axel), Leander, K. (Karin), Virani, S.S. (Salim), Kaminski, K.A. (Karol A.), Muehlschlegel, J.D. (Jochen), Allayee, H. (Hooman), Almgren, P. (Peter), Alver, M. (Maris), Baranova, E.V. (Ekaterina V.), Behloui, H. (Hassan), Boeckx, B. (Bram), Braund, P.S. (Peter), Breitling, L.P. (Lutz), Delgado, G., Duarte, N.E. (Nubia E.), Dubé, G.P. (Gregory), Dufresne, L. (Line), Eriksson, N. (Niclas), Foco, L. (Luisa), Scholz, M. (Markus), Gijsberts, C.M. (Crystel M.), Glinge, C. (Charlotte), Gong, Y. (Yan), Hartiala, J. (Jaana), Heydarpour, M. (Mahyar), Hubacek, J.A. (Jaroslav A.), Kleber, M.E. (Marcus), Kofink, D. (Daniel), Kotti, S. (Salma), Kuukasjärvi, P. (Pekka), Lee, V.-V. (Vei-Vei), Leiherer, A. (Andreas), Lenzini, P.A. (Petra A.), Levin, D. (Daniel), Lyytikäinen, L.-P. (Leo-Pekka), Martinelli, N. (Nicola), Mons, U. (Ute), Nelson, C.P. (Christopher P.), Nikus, K. (Kjell), Pilbrow, A.P. (Anna P.), Ploski, R. (Rafal), Sun, Y.V. (Yan V.), Tanck, M.W.T. (Michael), Tang, W. (W.), Trompet, S. (Stella), van der Laan, S.W. (Sander W.), Setten, J. (Jessica) van, Vilmundarson, R.O. (Ragnar O.), Viviani Anselmi, C. (Chiara), Vlachopoulou, E. (Efthymia), Al Ali, L. (Lawien), Boerwinkle, E.A. (Eric), Briguori, C. (Carlo), Carlquist, J.F. (John), Carruthers, K.F. (Kathryn), Casu, G. (Gavino), Deanfield, J. (John), Deloukas, P. (Panos), Dudbridge, F. (Frank), Engstrøm, T. (Thomas), Fitzpatrick, N. (Natalie), Fox, K.M. (Kim), Gigante, B. (Bruna), James, S.K. (Stefan), Lokki, M.-L. (Marja-Liisa), Lotufo, P.A. (Paulo A.), Marziliano, N. (Nicola), Mordi, I.R. (Ify R.), Muhlestein, J.B. (Joseph), Newton-Cheh, C. (Christopher), Pitha, J. (Jan), Saely, C.H. (Christoph H.), Samman-Tahhan, A. (Ayman), Sandesara, P.B. (Pratik B.), Teren, A. (Andrej), Timmis, A. (Adam), Van de Werf, F. (Frans), Wilde, A.A.M. (Arthur), Ford, I. (Ian), Stott, D.J. (David. J.), Algra, A. (Ale), Andreassi, M.G. (Maria G.), Ardissino, D. (Diego), Arsenault, B.J. (Benoit J.), Ballantyne, C. (Christie), Bergmeijer, T.O. (Thomas O.), Bezzina, C.R. (Connie R.), Body, S.C. (Simon C.), Boersma, E.H. (Eric H.), Bogaty, P. (Peter), Bots, M.L. (Michiel), Brenner, H. (Hermann), Brugts, J.J. (Jasper), Burkhardt, R. (Ralph), Carpeggiani, C. (Clara), Condorelli, G. (Gianluigi), Cooper-Dehoff, R.M. (Rhonda), Cresci, S. (Sharon), Danchin, N. (Nicolas), Faire, U. (Ulf) de, Doughty, R.N. (Robert N.), Drexel, H. (Heinz), Engert, J.C. (James C.), Fox, K.A.A. (Keith), Girelli, D. (Domenico), Grobbee, D.E. (Diederick E.), Hagström, E. (Emil), Hazen, S.L. (Stanley), Held, C. (Claes), Hemingway, H., Hoefer, I.E. (Imo), Hovingh, G.K. (G Kees), Jabbari, R. (Reza), Johnson, J.A. (Jennifer ), Jukema, J.W. (Jan Wouter), Kaczor, M.P. (Marcin P.), Kähönen, M. (Mika), Kettner, J. (Jiri), Kiliszek, M. (Marek), Klungel, O.H. (Olaf), Lagerqvist, B. (Bo), Lambrechts, D. (Diether), Laurikka, J.O. (Jari O.), Lehtimäki, T. (Terho), Lindholm, D. (Daniel), Mahmoodi, B.K. (Bakhtawar K.), Maitland-van der Zee, A-H. (Anke-Hilse), McPherson, R. (Ruth), Melander, O. (Olle), Metspalu, A. (Andres), Niemcunowicz-Janica, A. (Anna), Olivieri, O. (Oliviero), Opolski, G. (Grzegorz), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Pepine, C.J. (Carl), Pereira, A. (A.), Pilote, L. (Louise), Erdmann, J. (Jeanette), Richards, A.M. (A Mark), Sanak, M. (Marek), Siegbahn, A. (Agneta), Simon, T. (Tabassome), Sinisalo, J. (Juha), Smith, J.G. (J Gustav), Schwartz, S.M. (Stephen), Stender, S. (Steen), Stewart, A.F. (Alexandre F.), Szczeklik, W. (Wojciech), Szpakowicz, A. (Anna), Tardif, J.-C. (Jean-Claude), Berg, J.M. (Jurrien) ten, Tfelt-Hansen, J. (Jacob), Thanassoulis, G. (George), Thiery, J.P. (Joachim), Torp-Pedersen, C. (Christian Tobias), Graaf, Y. (Yolanda) van der, Visseren, F.L.J. (Frank), Waltenberger, J. (Johannes), Weeke, P.E. (Peter E.), Harst, P. (Pim) van der, Lang, C.C. (Chim C.), Sattar, N. (Naveed), Cameron, V.A. (Vicky A.), Anderson, J.L. (Jeffrey), Brophy, J.M. (James M.), Pare, G. (Guillame), Horne, B.D. (Benjamin), Ye, S. (Shu), Wallentin, L. (Lars), Wauters, E. (Els), Samani, N.J. (Nilesh), Hingorani, A. (Aroon), and Asselbergs, F.W. (Folkert)

Abstract

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants a

Published
2019
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33. Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study

Author

Universitat Rovira i Virgili, Huang T, Wang T, Zheng Y, Ellervik C, Li X, Gao M, Fang Z, Chai JF, Ahluwalia TVS, Wang Y, Voortman T, Noordam R, Frazier-Wood A, Scholz M, Sonestedt E, Akiyama M, Dorajoo R, Zhou A, Kilpeläinen TO, Kleber ME, Crozier SR, Godfrey KM, Lemaitre R, Felix JF, Shi Y, Gupta P, Khor CC, Lehtimäki T, Wang CA, Tiesler CMT, Thiering E, Standl M, Rzehak P, Marouli E, He M, Lecoeur C, Corella D, Lai CQ, Moreno LA, Pitkänen N, Boreham CA, Zhang T, Saw SM, Ridker PM, Graff M, van Rooij FJA, Uitterlinden AG, Hofman A, van Heemst D, Rosendaal FR, de Mutsert R, Burkhardt R, Schulz CA, Ericson U, Kamatani Y, Yuan JM, Power C, Hansen T, Sørensen TIA, Tjønneland A, Overvad K, Delgado G, Cooper C, Djousse L, Rivadeneira F, Jameson K, Zhao W, Liu J, Lee NR, Raitakari O, Kähönen M, Viikari J, Grote V, Langhendries JP, Koletzko B, Escribano J, Verduci E, Dedoussis G, Yu C, Tham YC, Lim B, Lim SH, Froguel P, Balkau B, Fink NR, Vinding RK, Sevelsted A, Bisgaard H, Coltell O, Dallongeville J, Gottrand F, Pahkala K, Niinikoski H, Hyppönen E, Pedersen O, März W, Inskip H, Jaddoe VWV, Dennison E, Wong TY, Sabanayagam C, Tai ES, Mohlke KL, Mackey DA, Gruszfeld D, Deloukas P, Tucker KL, Fumeron F, Bønnelykke K, Rossing P, Estruch R, Ordovas JM, Arnett DK, Meirhaeghe A, Amouyel P, Cheng CY, Sim X, Teo YY, van Dam RM, Koh WP, Orho-Melander M, Loeffler M, Kubo M, Thiery J, Mook-Kanamori DO, Mozaffarian D, Psaty BM, Franco OH, Wu T, North KE, Davey Smith G, Chavarro JE, Chasman DI, Qi L BIRTH-GENE (BIG) Study Working Group, Universitat Rovira i Virgili, and Huang T, Wang T, Zheng Y, Ellervik C, Li X, Gao M, Fang Z, Chai JF, Ahluwalia TVS, Wang Y, Voortman T, Noordam R, Frazier-Wood A, Scholz M, Sonestedt E, Akiyama M, Dorajoo R, Zhou A, Kilpeläinen TO, Kleber ME, Crozier SR, Godfrey KM, Lemaitre R, Felix JF, Shi Y, Gupta P, Khor CC, Lehtimäki T, Wang CA, Tiesler CMT, Thiering E, Standl M, Rzehak P, Marouli E, He M, Lecoeur C, Corella D, Lai CQ, Moreno LA, Pitkänen N, Boreham CA, Zhang T, Saw SM, Ridker PM, Graff M, van Rooij FJA, Uitterlinden AG, Hofman A, van Heemst D, Rosendaal FR, de Mutsert R, Burkhardt R, Schulz CA, Ericson U, Kamatani Y, Yuan JM, Power C, Hansen T, Sørensen TIA, Tjønneland A, Overvad K, Delgado G, Cooper C, Djousse L, Rivadeneira F, Jameson K, Zhao W, Liu J, Lee NR, Raitakari O, Kähönen M, Viikari J, Grote V, Langhendries JP, Koletzko B, Escribano J, Verduci E, Dedoussis G, Yu C, Tham YC, Lim B, Lim SH, Froguel P, Balkau B, Fink NR, Vinding RK, Sevelsted A, Bisgaard H, Coltell O, Dallongeville J, Gottrand F, Pahkala K, Niinikoski H, Hyppönen E, Pedersen O, März W, Inskip H, Jaddoe VWV, Dennison E, Wong TY, Sabanayagam C, Tai ES, Mohlke KL, Mackey DA, Gruszfeld D, Deloukas P, Tucker KL, Fumeron F, Bønnelykke K, Rossing P, Estruch R, Ordovas JM, Arnett DK, Meirhaeghe A, Amouyel P, Cheng CY, Sim X, Teo YY, van Dam RM, Koh WP, Orho-Melander M, Loeffler M, Kubo M, Thiery J, Mook-Kanamori DO, Mozaffarian D, Psaty BM, Franco OH, Wu T, North KE, Davey Smith G, Chavarro JE, Chasman DI, Qi L BIRTH-GENE (BIG) Study Working Group

Abstract

Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose

Published
2019

34. Low energy plasma analyzer

Author

Hardy, David A., Walton, D.M., Johnstone, A.D., Smith, M.F., Gough, M.P., Huber, A., Pantazis, J., and Burkhardt, R.

Subjects
Particles (Nuclear physics) -- Research, Plasma (Ionized gases) -- Research, Business, Electronics, Electronics and electrical industries
Published
1993

37. Nat Commun

Author

Franceschini, N., GIAMBARTOLOMEI, C., DE VRIES, P. S., FINAN, C., BIS, J. C., HUNTLEY, R. P., LOVERING, R. C., TAJUDDIN, S. M., WINKLER, T. W., GRAFF, M., KAVOUSI, M., Dale, C., SMITH, A. V., Hofer, E., VAN LEEUWEN, E. M., Nolte, I. M., Lu, L., Scholz, M., Sargurupremraj, Muralidharan, PITKANEN, N., FRANZEN, O., Joshi, P. K., NOORDAM, R., MARIONI, R. E., Hwang, S. J., MUSANI, S. K., SCHMINKE, U., PALMAS, W., ISAACS, A., CORREA, A., ZONDERMAN, A. B., Hofman, A., TEUMER, A., COX, A. J., UITTERLINDEN, A. G., Wong, A., SMIT, A. J., NEWMAN, A. B., Britton, A., RUUSALEPP, A., Sennblad, B., HEDBLAD, B., PASANIUC, B., PENNINX, B. W., LANGEFELD, C. D., WASSEL, C. L., Tzourio, Christophe, Fava, C., BALDASSARRE, D., O'LEARY, D. H., TEUPSER, D., Kuh, D., TREMOLI, E., MANNARINO, E., Grossi, E., BOERWINKLE, E., SCHADT, E. E., INGELSSON, E., VEGLIA, F., Rivadeneira, F., BEUTNER, F., Chauhan, Ganesh, Heiss, G., SNIEDER, H., Campbell, H., VOLZKE, H., MARKUS, H. S., DEARY, I. J., JUKEMA, J. W., de Graaf, J., Price, J., POTT, J., HOPEWELL, J. C., Liang, J., Thiery, J., Engmann, J., GERTOW, K., Rice, K., TAYLOR, K. D., DHANA, K., KIEMENEY, Lalm, LIND, L., RAFFIELD, L. M., LAUNER, L. J., HOLDT, L. M., DORR, M., DICHGANS, M., TRAYLOR, M., SITZER, M., KUMARI, M., Kivimaki, M., Nalls, M. A., MELANDER, O., RAITAKARI, O., FRANCO, O. H., RUEDA-OCHOA, O. L., ROUSSOS, P., WHINCUP, P. H., Amouyel, P., Giral, P., ANUGU, P., WONG, Q., Malik, R., RAURAMAA, R., BURKHARDT, R., Hardy, R., Schmidt, R., DE MUTSERT, R., MORRIS, R. W., STRAWBRIDGE, R. J., WANNAMETHEE, S. G., HAGG, S., Shah, S., MCLACHLAN, S., TROMPET, S., SESHADRI, S., KURL, S., HECKBERT, S. R., Ring, S., HARRIS, T. B., LEHTIMAKI, T., GALESLOOT, T. E., Shah, T., DE FAIRE, U., Plagnol, V., ROSAMOND, W. D., Post, W., Zhu, X., Zhang, X., Guo, X., SABA, Y., DEHGHAN, A., SELDENRIJK, A., MORRISON, A. C., HAMSTEN, A., PSATY, B. M., VAN DUIJN, C. M., LAWLOR, D. A., MOOK-KANAMORI, D. O., BOWDEN, D. W., Schmidt, H., WILSON, J. F., ROTTER, J. I., WARDLAW, J. M., DEANFIELD, J., HALCOX, J., LYYTIKAINEN, L. P., Loeffler, M., EVANS, M. K., Debette, Stéphanie, HUMPHRIES, S. E., VOLKER, U., GUDNASON, V., HINGORANI, A. D., BJORKEGREN, J. L. M., CASAS, J. P., O'DONNELL, C. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
VINTAGE, cardiovascular system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, cardiovascular diseases, HEALTHY
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018
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38. The RNA binding protein HuR is a master regulator of hepatic-lipid homeostasis

Author

Subramanian, P, additional, Grzybek, M, additional, Palladini, A, additional, Sinha, A, additional, Gargani, S, additional, Mitroulis, I, additional, Lesche, M, additional, Burkhardt, R, additional, Brosch, M, additional, Techritz, N, additional, Witt, A, additional, Chung, KJ, additional, Nati, M, additional, Dahl, A, additional, Mirtschink, P, additional, Zamboni, N, additional, Coskun, Ü, additional, Hampe, J, additional, Kontoyiannis, D, additional, and Chavakis, T, additional

Published
2019
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40. Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis

Author

Rosendahl, J. (Jonas), Kirsten, H. (Holger), Hegyi, E. (Eszter), Kovacs, P. (Peter), Weiss, F.U. (Frank-Ulrich), Laumen, H. (Helmut), Lichtner, P. (Peter), Ruffert, C. (Claudia), Chen, J.-M. (Jian-Min), Masson, E. (Emmanuelle), Beer, S. (Sebastian), Zimmer, C. (Constantin), Seltsam, K. (Katharina), Algül, H. (Hana), Bühler, F. (Florence), Bruno, M.J. (Marco), Bugert, P. (Peter), Burkhardt, R. (Ralph), Cavestro, G.M. (Giulia Martina), Cichoz-Lach, H. (Halina), Farré, A. (Antoni), Frank, J. (Josef), Gambaro, G. (Giovanni), Gimpfl, S. (Sebastian), Grallert, H. (Harald), Griesmann, H. (Heidi), Grützmann, R. (Robert), Hellerbrand, C. (Claus), Hegyi, P. (Peter), Hollenbach, M. (Marcus), Iordache, S. (Sevastitia), Jurkowska, G. (Grazyna), Keim, V. (Volker), Kiefer, F. (Falk), Krug, S. (Sebastian), Landt, O., Leo, M.D. (Milena Di), Lerch, M. (M.), Lévy, P. (Philippe), Löffler, M. (Markus), Löhr, M. (M.), Ludwig, M. (Maren), Macek, M. (Milan MI), Malats, N. (Núria), Malecka-Panas, E. (Ewa), Malerba, G. (Giovanni), Mann, K. (Karl), Mayerle, J. (Julia), Mohr, S. (Sonja), Te Morsche, R.H.M. (René H.), Motyka, M. (Marie), Mueller, S. (Sebastian), Müller, T. (Thomas), Nöthen, M.M. (Markus), Pedrazzoli, S. (Sergio), Pereira, S.P. (Stephen P.), Peters, A. (Annette), Pfützer, R. (Roland), Real, F.X. (Francisco), Rebours, V. (Vinciane), Ridinger, M. (Monika), Rietschel, M. (Marcella), Rösmann, E. (Eva), Saftoiu, A. (Adrian), Schneider, A. (Alexander), Schulz, H.-U. (Hans-Ulrich), Soranzo, N. (Nicole), Soyka, M. (Michael), Simon, P. (Peter), Skipworth, J. (James), Stickel, F. (Felix), Strauch, K. (Konstantin), Stumvoll, M. (Michael), Testoni, P.A. (Pier Alberto), Tönjes, A. (Anke), Werner, L. (Lena), Werner, J. (Jens Martin), Wodarz, N. (Norbert), Ziegler, M. (Martin), Masamune, A. (Atsushi), Mössner, J. (Joachim), Férec, C. (Claude), Michl, P. (Patrick), Drenth, J.P.H. (Joost), Witt, H. (Heiko), Scholz, M. (Markus), Sahin-Tóth, M. (Miklós), Rosendahl, J. (Jonas), Kirsten, H. (Holger), Hegyi, E. (Eszter), Kovacs, P. (Peter), Weiss, F.U. (Frank-Ulrich), Laumen, H. (Helmut), Lichtner, P. (Peter), Ruffert, C. (Claudia), Chen, J.-M. (Jian-Min), Masson, E. (Emmanuelle), Beer, S. (Sebastian), Zimmer, C. (Constantin), Seltsam, K. (Katharina), Algül, H. (Hana), Bühler, F. (Florence), Bruno, M.J. (Marco), Bugert, P. (Peter), Burkhardt, R. (Ralph), Cavestro, G.M. (Giulia Martina), Cichoz-Lach, H. (Halina), Farré, A. (Antoni), Frank, J. (Josef), Gambaro, G. (Giovanni), Gimpfl, S. (Sebastian), Grallert, H. (Harald), Griesmann, H. (Heidi), Grützmann, R. (Robert), Hellerbrand, C. (Claus), Hegyi, P. (Peter), Hollenbach, M. (Marcus), Iordache, S. (Sevastitia), Jurkowska, G. (Grazyna), Keim, V. (Volker), Kiefer, F. (Falk), Krug, S. (Sebastian), Landt, O., Leo, M.D. (Milena Di), Lerch, M. (M.), Lévy, P. (Philippe), Löffler, M. (Markus), Löhr, M. (M.), Ludwig, M. (Maren), Macek, M. (Milan MI), Malats, N. (Núria), Malecka-Panas, E. (Ewa), Malerba, G. (Giovanni), Mann, K. (Karl), Mayerle, J. (Julia), Mohr, S. (Sonja), Te Morsche, R.H.M. (René H.), Motyka, M. (Marie), Mueller, S. (Sebastian), Müller, T. (Thomas), Nöthen, M.M. (Markus), Pedrazzoli, S. (Sergio), Pereira, S.P. (Stephen P.), Peters, A. (Annette), Pfützer, R. (Roland), Real, F.X. (Francisco), Rebours, V. (Vinciane), Ridinger, M. (Monika), Rietschel, M. (Marcella), Rösmann, E. (Eva), Saftoiu, A. (Adrian), Schneider, A. (Alexander), Schulz, H.-U. (Hans-Ulrich), Soranzo, N. (Nicole), Soyka, M. (Michael), Simon, P. (Peter), Skipworth, J. (James), Stickel, F. (Felix), Strauch, K. (Konstantin), Stumvoll, M. (Michael), Testoni, P.A. (Pier Alberto), Tönjes, A. (Anke), Werner, L. (Lena), Werner, J. (Jens Martin), Wodarz, N. (Norbert), Ziegler, M. (Martin), Masamune, A. (Atsushi), Mössner, J. (Joachim), Férec, C. (Claude), Michl, P. (Patrick), Drenth, J.P.H. (Joost), Witt, H. (Heiko), Scholz, M. (Markus), and Sahin-Tóth, M. (Miklós)

Abstract

Objective: Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus. Design: 1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used. Results: We replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk. Conclusion: An inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.

Published
2018
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41. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), Morris, R.W. (Richard), Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), and Morris, R.W. (Richard)

Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018
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42. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkanen, N, Franzen, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, S-J, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O'Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Voelzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Doer, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, de Mutsert, R, Morris, RW, Strawbridge, RJ, Wannamethee, SG, Hagg, S, Shah, S, McLachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, SR, Ring, S, Harris, TB, Lehtimaki, T, Galesloot, TE, Shah, T, de Faire, U, Plagnol, V, Rosamond, WD, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, AC, Hamsten, A, Psaty, BM, van Duijn, CM, Lawlor, DA, Mook-Kanamori, DO, Bowden, DW, Schmidt, H, Wilson, JF, Wilson, JG, Rotter, JI, Wardlaw, JM, Deanfield, J, Halcox, J, Lyytikainen, L-P, Loeffler, M, Evans, MK, Debette, S, Humphries, SE, Voelker, U, Gudnason, V, Hingorani, AD, Bjorkegren, JLM, Casas, JP, O'Donnell, CJ, Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkanen, N, Franzen, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, S-J, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O'Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Voelzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Doer, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, de Mutsert, R, Morris, RW, Strawbridge, RJ, Wannamethee, SG, Hagg, S, Shah, S, McLachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, SR, Ring, S, Harris, TB, Lehtimaki, T, Galesloot, TE, Shah, T, de Faire, U, Plagnol, V, Rosamond, WD, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, AC, Hamsten, A, Psaty, BM, van Duijn, CM, Lawlor, DA, Mook-Kanamori, DO, Bowden, DW, Schmidt, H, Wilson, JF, Wilson, JG, Rotter, JI, Wardlaw, JM, Deanfield, J, Halcox, J, Lyytikainen, L-P, Loeffler, M, Evans, MK, Debette, S, Humphries, SE, Voelker, U, Gudnason, V, Hingorani, AD, Bjorkegren, JLM, Casas, JP, and O'Donnell, CJ

Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018

43. Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis

Author

Rosendahl, J, Kirsten, H, Hegyi, E, Kovacs, P, Weiss, FU, Laumen, H, Lichtner, P, Ruffert, C, Chen, JM, Masson, E, Beer, S, Zimmer, C, Seltsam, K, Alguel, H, Buehler, F, Bruno, Marco, Bugert, P, Burkhardt, R, Cavestro, GM, Cichoz-Lach, H, Farre, A, Frank, J, Gambaro, G, Gimpfl, S, Grallert, H, Griesmann, H, Gruetzmann, R, Hellerbrand, C, Hegyi, P, Hollenbach, M, Iordache, S, Jurkowska, G, Keim, V, Kiefer, F, Krug, S, Landt, O, De Leo, M, Lerch, MM, Levy, P, Loeffler, M, Loehr, M, Ludwig, M, Macek, M, Malats, N, Malecka-Panas, E, Malerba, G, Mann, K, Mayerle, J, Mohr, S, te Morsche, RHM, Motyka, M, Mueller, S, Mueller, T, Noethen, MM, Pedrazzoli, S, Pereira, SP, Peters, A, Pfuetzer, R, Real, FX, Rebours, V, Ridinger, M, Rietschel, M, Roesmann, E, Saftoiu, A, Schneider, A, Schulz, HU, Soranzo, N, Soyka, M, Simon, P, Skipworth, J, Stickel, F, Strauch, K, Stumvoll, M, Testoni, PA, Toenjes, A, Werner, L, Werner, J, Wodarz, N, Ziegler, M, Masamune, A, Moessner, J, Ferec, C, Michl, P, Drenth, JPH, Witt, H, Scholz, M, Sahin-Toth, M, Rosendahl, J, Kirsten, H, Hegyi, E, Kovacs, P, Weiss, FU, Laumen, H, Lichtner, P, Ruffert, C, Chen, JM, Masson, E, Beer, S, Zimmer, C, Seltsam, K, Alguel, H, Buehler, F, Bruno, Marco, Bugert, P, Burkhardt, R, Cavestro, GM, Cichoz-Lach, H, Farre, A, Frank, J, Gambaro, G, Gimpfl, S, Grallert, H, Griesmann, H, Gruetzmann, R, Hellerbrand, C, Hegyi, P, Hollenbach, M, Iordache, S, Jurkowska, G, Keim, V, Kiefer, F, Krug, S, Landt, O, De Leo, M, Lerch, MM, Levy, P, Loeffler, M, Loehr, M, Ludwig, M, Macek, M, Malats, N, Malecka-Panas, E, Malerba, G, Mann, K, Mayerle, J, Mohr, S, te Morsche, RHM, Motyka, M, Mueller, S, Mueller, T, Noethen, MM, Pedrazzoli, S, Pereira, SP, Peters, A, Pfuetzer, R, Real, FX, Rebours, V, Ridinger, M, Rietschel, M, Roesmann, E, Saftoiu, A, Schneider, A, Schulz, HU, Soranzo, N, Soyka, M, Simon, P, Skipworth, J, Stickel, F, Strauch, K, Stumvoll, M, Testoni, PA, Toenjes, A, Werner, L, Werner, J, Wodarz, N, Ziegler, M, Masamune, A, Moessner, J, Ferec, C, Michl, P, Drenth, JPH, Witt, H, Scholz, M, and Sahin-Toth, M

Published
2018

44. Digitally Controlled Acoustic-Testing System

Author

Shah, K. C and Burkhardt, R

Subjects
Electronic Systems
Abstract

Digital electronic control system developed for use in effecting accurate, real-time, closed-loop control of large acoustic test facility. Installation of system incorporates state-of-the-art technology to optimize shaping of acoustic spectrum and controlling operation of equipment in large reverberant chamber to degree not possible with open-loop manual control.

Published
1994

45. Cable compliance

Author

Kerley, J, Eklund, W, Burkhardt, R, and Rossoni, P

Subjects
Engineering (General)
Abstract

The object of the investigation was to solve mechanical problems using cable-in-bending and cable-in-torsion. These problems included robotic contacts, targets, and controls using cable compliance. Studies continued in the use of cable compliance for the handicapped and the elderly. These included work stations, walkers, prosthetic knee joints, elbow joints, and wrist joints. More than half of these objects were met, and models were made and studies completed on most of the others. It was concluded that the many different and versatile solutions obtained only opened the door to many future challenges.

Published
1992

46. PO-1035: Detection of radiation induced lung fibrosis using x-ray dark-field imaging in a murine model

Author

Gora, T., primary, Burkhardt, R., additional, Umkehrer, S., additional, Herzen, J., additional, Schilling, D., additional, Feuchtinger, A., additional, Walch, A.K., additional, Schmid, T.E., additional, Multhoff, G., additional, Noël, P.B., additional, Rummeny, E.J., additional, Pfeiffer, F., additional, Combs, S.E., additional, and Wilkens, J.J., additional

Published
2018
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47. 195PR interval prolongation as intermediate phenotype for atrial fibrillation: Association with echocardiographic parameters and biomarkers (the LIFE-Adult-Study)

Author

Zeynalova, S, primary, Kornej, J, additional, Loeffler, M, additional, Tautenhahn, S, additional, Stoebe, S, additional, Thiery, J, additional, Engel, C H, additional, Wirkner, K, additional, Burkhardt, R, additional, Baber, R, additional, Husser, D, additional, and Hagendorff, A, additional

Published
2018
Full Text
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