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1. A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression.

Author

Yasukazu Makino, Tadashi Konoshita, Atsuhito Omori, Nobuhiro Maegawa, Takahiro Nakaya, Mai Ichikawa, Katsushi Yamamoto, Shigeyuki Wakahara, Tamotsu Ishizuka, Tamehito Onoe, Hiroyuki Nakamura, and Genomic Disease Outcome Consortium (G-DOC) Study Investigators

Subjects
Medicine, Science
Abstract

The high heritability of plasma renin activity was confirmed in recent investigations. A variation located near the strong enhancer of the human renin gene (REN), C-5312T, has been shown to have different transcription activity levels depending on its allele: the 5312T allele shows transcription levels that are 45% greater than those of the 5312C allele. The purpose of this study was to confirm the hypothesis that variations in the enhancer region of the REN gene are involved in regulating renal expression of renin.Sixty-four subjects with biopsy-proven renal diseases were included in this study (male/female: 35/29, age 41.9 ± 20.9 years, SBP/DBP 123.1 ± 23.7/73.4 ± 14.8 mmHg, s-Cr 0.93 ± 0.63 mg/dl). A genetic variant of REN, C-5312T, was assayed by PCR-RFLP and the TaqMan method. Total RNAs from a small part of the renal cortex were reverse-transcribed and amplified for REN and GAPDH with a real-time PCR system.Logarithmically transformed expression values of the relative ratio of REN to GAPDH (10-3) were as follows (mean ± SE): CC (26 cases), 0.016 ± 0.005; CT (33 cases), 0.047 ± 0.021 (p = 0.41 vs. CC); TT (5 cases), 0.198 ± 0.194 (p = 0.011 vs. CC, p < 0.031 vs. CT). Thus, significant differences in REN expression were observed among the genetic variants.The results suggest that variants in the enhancer region of the human renin gene have an effect on the expression levels of renin in renal tissue; this observation is in good accordance with the results of the transcriptional assay.

Published
2015
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3. Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severely Impaired Spermatogenesis Leading to Male Infertility

Author

Wyrwoll, Margot J., Temel, Sehime G., Nagirnaja, Liina, Oud, Manon S., Lopes, Alexandra M., van der Heijden, Godfried W., Heald, James S., Rotte, Nadja, Wistuba, Joachim, Woeste, Marius, Ledig, Susanne, Krenz, Henrike, Smits, Roos M., Carvalho, Filipa, Goncalves, Joao, Fietz, Daniela, Turkgenc, Burcu, Ergoren, Mahmut C., Cetinkaya, Murat, Basar, Murad, Kahraman, Semra, McEleny, Kevin, Xavier, Miguel J., Turner, Helen, Pilatz, Adrian, Roepke, Albrecht, Dugas, Martin, Kliesch, Sabine, Neuhaus, Nina, Aston I, Kenneth, Conrad, Donald F., Veltman, Joris A., Friedrich, Corinna, Tuettelmann, Frank, Consortium, G. E. M. I. N. I., Acibadem University Dspace, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı., Temel, Şehime, and AAG-8385-2021

Subjects
0301 basic medicine, Male, Turkey, Male Infertility, Azoospermia, Y Chromosome, Mouse, Genetic code, M1AP, Procedures, Gene, Male infertility, Mice, 0302 clinical medicine, Turkey (bird), Testis, Missense mutation, Spermatid, Genetics (clinical), Priority journal, Genetics, Allele, 030219 obstetrics & reproductive medicine, Genetics & heredity, Homozygote, Variants, Phenotype, Cryptozoospermia, Spermatozoa, Turkish citizen, Non-obstructive azoospermia (NOA), Meiosis, Germ cell, Human, Infertility, Adult, Spermatozoon, Biology, Article, Frameshift mutation, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Cell cycle arrest, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Cell cycle checkpoints, Report, Exome Sequencing, medicine, Animals, Humans, Family, MaleI Infertility, Gene mutation, Spermatogenesis, Disease severity, Alleles, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Animal, Protein, Whole exome sequencing, Proteins, In vitro study, Oligospermia, Cell Cycle Checkpoints, medicine.disease, Infertility, male, Nonhuman, Doenças Genéticas, Meiosis 1 arresting protein, mouse, 030104 developmental biology, Mutation, Loss of function mutation, Genetic association, M1AP gene, Genetic variability, Cell cycle checkpoint
Abstract

Male infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity. This work was carried out within the frame of the German Research Foundation Clinical Research Unit ‘‘Male Germ Cells: from Genes to Function’’ (DFG CRU326). Funding for sequencing of the GEMINI cohort was provided by the National Institutes of Health, United States (R01HD078641). The analyses in the Turkish family were supported by a grant from the Bursa University of Uludag Project Unit [KUAP(T)-2014/36]. info:eu-repo/semantics/publishedVersion

Published
2020

4. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimerʼs disease

Author

Lambert, J-C, Grenier-Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K, Ikram, M A, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz-Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, J-F, Tzourio, C, Berr, C, Schrijvers, E MC, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, C A, Lannfelt, L, Ingelsson, M, Prince, J A, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossù, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez-Garcia, F, Del Zompo, M, Coto, E, Owen, M, OʼDonovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buée, L, Campion, D, Soininen, H, Breteler, M, Riemenschneider, M, Van Broeckhoven, C, Alpérovitch, A, Lathrop, M, Trégouët, D-A, Williams, J, Amouyel, P, consortium, E ADI, and consortium, G ERAD

Published
2013
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5. INTEGRATIVE GENOMICS LINKS HOMEOBOX TRANSCRIPTION FACTORS TO INTRA-ABDOMINAL OBESITY: 15 invited speake

Author

Dankel, S., Fadnes, D. J., Christoforou, A., Mathieson, I., Haugen, C., Røst, T. H., Claussnitzer, M., Hauner, H., Laumen, H., Dalkilic-Liddle, I., Seed, B., Gudbrandsen, O. A., Veum, V. L., Solsvik, M. H., Våge, V., Nielsen, Jørgen H., Busch, C., Liu, Y. J., Pei, Y. F., Deng, H. W., Scherag, A., Hinney, A., Hebebrand, J., Froguel, P., Meyre, D., Lindgren, C. M., Sagen, J. V., Steen, V. M., Mellgren, G., and Consortium, G.

Published
2012

9. Mining the human phenome using allelic scores that index biological intermediates

Author

Evans, D.M., Brion, M.J., Paternoster, L., Kemp, J.P., McMahon, G., Munafo, M., Whitfield, J.B., Medland, S.E., Montgomery, G.W., Consortium, G., Consortium, C.R.P., Consortium, T.A.G., Timpson, N.J., Pourcain, B. St, Lawlor, D.A., Martin, N.G., Dehghan, A., Hirschhorn, J., Smith, G., and Kiemeney, L.A.L.M.

Subjects
Aetiology, screening and detection [ONCOL 5], Molecular epidemiology Aetiology, screening and detection [NCEBP 1]
Abstract

Contains fulltext : 125660.pdf (Publisher’s version ) (Open Access) It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections.

Published
2013

11. Multi-wavelength Observations of the Flaring Gamma-ray Blazar 3C 66A in 2008 October

Author

Abdo, A. A., Ackermann, M., Ajello, M., Baldini, L., Ballet, J., Barbiellini, G., Bastieri, D., Bechtol, K., Bellazzini, R., Berenji, B., Blandford, R. D., Bonamente, Emanuele, Borgland, A. W., Bouvier, A., Bregeon, J., Brez, A., Brigida, M., Bruel, P., Buehler, R., Buson, S., Caliandro, G. A., Cameron, R. A., Caraveo, P. A., Carrigan, S., Casandjian, J. M., Cavazzuti, E., Cecchi, Claudia, Çelik, Ö., Charles, E., Chekhtman, A., Cheung, C. C., Chiang, J., Ciprini, S., Claus, R., Cohen Tanugi, J., Conrad, J., Costamante, L., Cutini, S., Davis, D. S., Dermer, C. D., Palma, F. d., Digel, S. W., Couto, E. d., Drell, P. S., Dubois, R., Dumora, D., Favuzzi, C., Fegan, S. J., Fortin, P., Frailis, M., Fuhrmann, L., Fukazawa, Y., Funk, S., Fusco, P., Gargano, F., Gasparrini, D., Gehrels, N., Germani, S., Giglietto, N., Giommi, P., Giordano, F., Giroletti, M., Glanzman, T., Godfrey, G., Grenier, I. A., Grove, J. E., Guillemot, L., Guiriec, S., Hadasch, D., Hayashida, M., Hays, E., Horan, D., Hughes, R. E., Itoh, R., Jóhannesson, G., Johnson, A. S., Johnson, T. J., Johnson, W. N., Kamae, T., Katagiri, H., Kataoka, J., Knödlseder, J., Kuss, M., Lande, J., Latronico, L., Lee, S., Longo, F., Loparco, F., Lott, B., Lovellette, M. N., Lubrano, P., Makeev, A., Mazziotta, M. N., Mcenery, J. E., Mehault, J., Michelson, P. F., Mizuno, T., Moiseev, A. A., Monte, C., Monzani, M. E., Morselli, A., Moskalenko, I. V., Murgia, S., Nakamori, T., Naumann Godo, M., Nestoras, I., Nolan, P. L., Norris, J. P., Nuss, E., Ohsugi, T., Okumura, A., Omodei, N., Orlando, E., Ormes, J. F., Ozaki, M., Paneque, D., Panetta, J. H., Parent, D., Pelassa, V., Pepe, M., Pesce Rollins, M., Piron, F., Porter, T. A., Rainò, S., Rando, R., Razzano, M., Reimer, A., Reimer, O., Reyes, L. C., Ripken, J., Ritz, S., Romani, R. W., Roth, M., Sadrozinski, H. F., Sanchez, D., Sander, A., Scargle, J. D., Sgrò, C., Shaw, M. S., Smith, P. D., Spandre, G., Spinelli, P., Strickman, M. S., Suson, D. J., Takahashi, H., Tanaka, T., Thayer, J. B., Thayer, J. G., Thompson, D. J., Tibaldo, L., Torres, D. F., Tosti, Gino, Tramacere, A., Usher, T. L., Vandenbroucke, J., Vasileiou, V., Vilchez, N., Vitale, V., Waite, A. P., Wang, P., Winer, B. L., Wood, K. S., Yang, Z., Ylinen, T., Ziegler, M., Acciari, V. A., Aliu, E., Arlen, T., Aune, T., Beilicke, M., Benbow, W., Böttcher, M., Boltuch, D., Bradbury, S. M., Buckley, J. H., Bugaev, V., Byrum, K., Cannon, A., Cesarini, A., Christiansen, J. L., Ciupik, L., Cui, W., I. d., La, Dickherber, R., Errando, M., Falcone, A., Finley, J. P., Finnegan, G., Fortson, L., Furniss, A., Galante, N., Gall, D., Gillanders, G. H., Godambe, S., Grube, J., Guenette, R., Gyuk, G., Hanna, D., Holder, J., Hui, C. M., Humensky, T. B., Imran, A., Kaaret, P., Karlsson, N., Kertzman, M., Kieda, D., Konopelko, A., Krawczynski, H., Krennrich, F., Lang, M. J., Lebohec, S., Maier, G., Mcarthur, S., Mccann, A., Mccutcheon, M., Moriarty, P., Mukherjee, R., Ong, R. A., Otte, A. N., Pandel, D., Perkins, J. S., Pichel, A., Pohl, M., Quinn, J., Ragan, K., Reynolds, P. T., Roache, E., Rose, H. J., Schroedter, M., Sembroski, G. H., Senturk, G. D., Smith, A. W., Steele, D., Swordy, S. P., Tešić, G., Theiling, M., Thibadeau, S., Varlotta, A., Vassiliev, V. V., Vincent, S., Wakely, S. P., Ward, J. E., Weekes, T. C., Weinstein, A., Weisgarber, T., Williams, D. A., Wissel, S., Wood, M., Villata, M., Raiteri, C. M., Gurwell, M. A., Larionov, V. M., Kurtanidze, O. M., Aller, M. F., Lähteenmäki, A., Chen, W. P., Berduygin, A., Agudo, I., Aller, H. D., Arkharov, A. A., Bach, U., Bachev, R., Beltrame, P., Benítez, E., Buemi, C. S., Dashti, J., Calcidese, P., Capezzali, D., Carosati, D., Rio, D. D., Paola, A. D., Diltz, C., Dolci, M., Dultzin, D., Forné, E., Gómez, J. L., Hagen Thorn, V. A., Halkola, A., Heidt, J., Hiriart, D., Hovatta, T., Hsiao, H., Jorstad, S. G., Kimeridze, G. N., Konstantinova, T. S., Kopatskaya, E. N., Koptelova, E., Leto, P., Ligustri, R., Lindfors, E., Lopez, J. M., Marscher, A. P., Mommert, M., Mujica, R., Nikolashvili, M. G., Nilsson, K., Palma, N., Pasanen, M., Roca Sogorb, M., Ros, J. A., Roustazadeh, P., Sadun, A. C., Saino, J., Sigua, L. A., Sillanää, A., Sorcia, M., Takalo, L. O., Tornikoski, M., Trigilio, C., Turchetti, R., Umana, G., Belloni, T., Blake, C. H., Bloom, J. S., Angelakis, E., Fumagalli, M., Hauser, M., Prochaska, J. X., Riquelme, D., Sievers, A., Starr, D. L., Tagliaferri, G., Ungerechts, H., Wagner, S., Zensus, J. A., Collaboration, F. L., Collaboration, V., Consortium, G., Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Leprince-Ringuet (LLR), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Laboratoire de Physique Théorique et Astroparticules (LPTA), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre d'étude spatiale des rayonnements (CESR), Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Fermi-LAT, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Abdo, A. A., Ackermann, M., Ajello, M., Baldini, L., Ballet, J., Barbiellini, G., Bastieri, D., Bechtol, K., Bellazzini, R., Berenji, B., Blandford, R. D., Bonamente, E., Borgland, A. W., Bouvier, A., Bregeon, J., Brez, A., Brigida, M., Bruel, P., Buehler, R., Buson, S., Caliandro, G. A., Cameron, R. A., Caraveo, P. A., Carrigan, S., Casandjian, J. M., Cavazzuti, E., Cecchi, C., Çelik, Ö., Charles, E., Chekhtman, A., Cheung, C. C., Chiang, J., Ciprini, S., Claus, R., Cohen Tanugi, J., Conrad, J., Costamante, L., Cutini, S., Davis, D. S., Dermer, C. D., de Palma, F., Digel, S. W., do Couto, e. Silva E., Drell, P. S., Dubois, R., Dumora, D., Favuzzi, C., Fegan, S. J., Fortin, P., Frailis, M., Fuhrmann, L., Fukazawa, Y., Funk, S., Fusco, P., Gargano, F., Gasparrini, D., Gehrels, N., Germani, S., Giglietto, N., Giommi, P., Giordano, F., Giroletti, M., Glanzman, T., Godfrey, G., Grenier, I. A., Grove, J. E., Guillemot, L., Guiriec, S., Hadasch, D., Hayashida, M., Hays, E., Horan, D., Hughes, R. E., Itoh, R., Jóhannesson, G., Johnson, A. S., Johnson, T. J., Johnson, W. N., Kamae, T., Katagiri, H., Kataoka, J., Knödlseder, J., Kuss, M., Lande, J., Latronico, L., Lee, S. H., Longo, Francesco, Loparco, F., Lott, B., Lovellette, M. N., Lubrano, P., Makeev, A., Mazziotta, M. N., Mcenery, J. E., Mehault, J., Michelson, P. F., Mizuno, T., Moiseev, A. A., Monte, C., Monzani, M. E., Morselli, A., Moskalenko, I. V., Murgia, S., Nakamori, T., Naumann Godo, M., Nestoras, I., Nolan, P. L., Norris, J. P., Nuss, E., Ohsugi, T., Okumura, A., Omodei, N., Orlando, E., Ormes, J. F., Ozaki, M., Paneque, D., Panetta, J. H., Parent, D., Pelassa, V., Pepe, M., Pesce Rollins, M., Piron, F., Porter, T. A., Rainò, S., Rando, R., Razzano, M., Reimer, A., Reimer, O., Reyes, L. C., Ripken, J., Ritz, S., Romani, R. W., Roth, M., Sadrozinski, H. F. W., Sanchez, D., Sander, A., Scargle, J. D., Sgrò, C., Shaw, M. S., Smith, P. D., Spandre, G., Spinelli, P., Strickman, M. S., Suson, D. J., Takahashi, H., Tanaka, T., Thayer, J. B., Thayer, J. G., Thompson, D. J., Tibaldo, L., Torres, D. F., Tosti, G., Tramacere, A., Usher, T. L., Vandenbroucke, J., Vasileiou, V., Vilchez, N., Vitale, V., Waite, A. P., Wang, P., Winer, B. L., Wood, K. S., Yang, Z., Ylinen, T., Ziegler, M., Acciari, V. A., Aliu, E., Arlen, T., Aune, T., Beilicke, M., Benbow, W., Böttcher, M., Boltuch, D., Bradbury, S. M., Buckley, J. H., Bugaev, V., Byrum, K., Cannon, A., Cesarini, A., Christiansen, J. L., Ciupik, L., Cui, W., de la Calle Perez, I., Dickherber, R., Errando, M., Falcone, A., Finley, J. P., Finnegan, G., Fortson, L., Furniss, A., Galante, N., Gall, D., Gillanders, G. H., Godambe, S., Grube, J., Guenette, R., Gyuk, G., Hanna, D., Holder, J., Hui, C. M., Humensky, T. B., Imran, A., Kaaret, P., Karlsson, N., Kertzman, M., Kieda, D., Konopelko, A., Krawczynski, H., Krennrich, F., Lang, M. J., Lebohec, S., Maier, G., Mcarthur, S., Mccann, A., Mccutcheon, M., Moriarty, P., Mukherjee, R., Ong, R. A., Otte, A. N., Pandel, D., Perkins, J. S., Pichel, A., Pohl, M., Quinn, J., Ragan, K., Reynolds, P. T., Roache, E., Rose, H. J., Schroedter, M., Sembroski, G. H., Senturk G., Demet, Smith, A. W., Steele, D., Swordy, S. P., Tešić, G., Theiling, M., Thibadeau, S., Varlotta, A., Vassiliev, V. V., Vincent, S., Wakely, S. P., Ward, J. E., Weekes, T. C., Weinstein, A., Weisgarber, T., Williams, D. A., Wissel, S., Wood, M., Villata, M., Raiteri, C. M., Gurwell, M. A., Larionov, V. M., Kurtanidze, O. M., Aller, M. F., Lähteenmäki, A., Chen, W. P., Berduygin, A., Agudo, I., Aller, H. D., Arkharov, A. A., Bach, U., Bachev, R., Beltrame, P., Benítez, E., Buemi, C. S., Dashti, J., Calcidese, P., Capezzali, D., Carosati, D., Da Rio, D., Di Paola, A., Diltz, C., Dolci, M., Dultzin, D., Forné, E., Gómez, J. L., Hagen Thorn, V. A., Halkola, A., Heidt, J., Hiriart, D., Hovatta, T., Hsiao, H. Y., Jorstad, S. G., Kimeridze, G. N., Konstantinova, T. S., Kopatskaya, E. N., Koptelova, E., Leto, P., Ligustri, R., Lindfors, E., Lopez, J. M., Marscher, A. P., Mommert, M., Mujica, R., Nikolashvili, M. G., Nilsson, K., Palma, N., Pasanen, M., Roca Sogorb, M., Ros, J. A., Roustazadeh, P., Sadun, A. C., Saino, J., Sigua, L. A., Sillanää, A., Sorcia, M., Takalo, L. O., Tornikoski, M., Trigilio, C., Turchetti, R., Umana, G., Belloni, T., Blake, C. H., Bloom, J. S., Angelakis, E., Fumagalli, M., Hauser, M., Prochaska, J. X., Riquelme, D., Sievers, A., Starr, D. L., Tagliaferri, G., Ungerechts, H., Wagner, S., Zensus, J. A., Abdo, A, Ackermann, M, Ajello, M, Baldini, L, Ballet, J, Barbiellini, G, Bastieri, D, Bechtol, K, Bellazzini, R, Berenji, B, Blandford, R, Bonamente, E, Borgland, A, Bouvier, A, Bregeon, J, Brez, A, Brigida, M, Bruel, P, Buehler, R, Buson, S, Caliandro, G, Cameron, R, Caraveo, P, Carrigan, S, Casandjian, J, Cavazzuti, E, Cecchi, C, Celik, O, Charles, E, Chekhtman, A, Cheung, C, Chiang, J, Ciprini, S, Claus, R, Cohen-Tanugi, J, Conrad, J, Costamante, L, Cutini, S, Davis, D, Dermer, C, De Palma, F, Digel, S, Do Couto E Silva, E, Drell, P, Dubois, R, Dumora, D, Favuzzi, C, Fegan, S, Fortin, P, Frailis, M, Fuhrmann, L, Fukazawa, Y, Funk, S, Fusco, P, Gargano, F, Gasparrini, D, Gehrels, N, Germani, S, Giglietto, N, Giommi, P, Giordano, F, Giroletti, M, Glanzman, T, Godfrey, G, Grenier, I, Grove, J, Guillemot, L, Guiriec, S, Hadasch, D, Hayashida, M, Hays, E, Horan, D, Hughes, R, Itoh, R, Johannesson, G, Johnson, A, Johnson, T, Johnson, W, Kamae, T, Katagiri, H, Kataoka, J, Knodlseder, J, Kuss, M, Lande, J, Latronico, L, Lee, S, Longo, F, Loparco, F, Lott, B, Lovellette, M, Lubrano, P, Makeev, A, Mazziotta, M, Mcenery, J, Mehault, J, Michelson, P, Mizuno, T, Moiseev, A, Monte, C, Monzani, M, Morselli, A, Moskalenko, I, Murgia, S, Nakamori, T, Naumann-Godo, M, Nestoras, I, Nolan, P, Norris, J, Nuss, E, Ohsugi, T, Okumura, A, Omodei, N, Orlando, E, Ormes, J, Ozaki, M, Paneque, D, Panetta, J, Parent, D, Pelassa, V, Pepe, M, Pesce-Rollins, M, Piron, F, Porter, T, Raino, S, Rando, R, Razzano, M, Reimer, A, Reimer, O, Reyes, L, Ripken, J, Ritz, S, Romani, R, Roth, M, Sadrozinski, H, Sanchez, D, Sander, A, Scargle, J, Sgro, C, Shaw, M, Smith, P, Spandre, G, Spinelli, P, Strickman, M, Suson, D, Takahashi, H, Tanaka, T, Thayer, J, Thompson, D, Tibaldo, L, Torres, D, Tosti, G, Tramacere, A, Usher, T, Vandenbroucke, J, Vasileiou, V, Vilchez, N, Vitale, V, Waite, A, Wang, P, Winer, B, Wood, K, Yang, Z, Ylinen, T, Ziegler, M, Acciari, V, Aliu, E, Arlen, T, Aune, T, Beilicke, M, Benbow, W, Bottcher, M, Boltuch, D, Bradbury, S, Buckley, J, Bugaev, V, Byrum, K, Cannon, A, Cesarini, A, Christiansen, J, Ciupik, L, Cui, W, De La Calle Perez, I, Dickherber, R, Errando, M, Falcone, A, Finley, J, Finnegan, G, Fortson, L, Furniss, A, Galante, N, Gall, D, Gillanders, G, Godambe, S, Grube, J, Guenette, R, Gyuk, G, Hanna, D, Holder, J, Hui, C, Humensky, T, Imran, A, Kaaret, P, Karlsson, N, Kertzman, M, Kieda, D, Konopelko, A, Krawczynski, H, Krennrich, F, Lang, M, Lebohec, S, Maier, G, Mcarthur, S, Mccann, A, Mccutcheon, M, Moriarty, P, Mukherjee, R, Ong, R, Otte, A, Pandel, D, Perkins, J, Pichel, A, Pohl, M, Quinn, J, Ragan, K, Reynolds, P, Roache, E, Rose, H, Schroedter, M, Sembroski, G, Senturk, G, Smith, A, Steele, D, Swordy, S, Tesic, G, Theiling, M, Thibadeau, S, Varlotta, A, Vassiliev, V, Vincent, S, Wakely, S, Ward, J, Weekes, T, Weinstein, A, Weisgarber, T, Williams, D, Wissel, S, Wood, M, Villata, M, Raiteri, C, Gurwell, M, Larionov, V, Kurtanidze, O, Aller, M, Lahteenmaki, A, Chen, W, Berduygin, A, Agudo, I, Aller, H, Arkharov, A, Bach, U, Bachev, R, Beltrame, P, Benitez, E, Buemi, C, Dashti, J, Calcidese, P, Capezzali, D, Carosati, D, Da Rio, D, Di Paola, A, Diltz, C, Dolci, M, Dultzin, D, Forne, E, Gomez, J, Hagen-Thorn, V, Halkola, A, Heidt, J, Hiriart, D, Hovatta, T, Hsiao, H, Jorstad, S, Kimeridze, G, Konstantinova, T, Kopatskaya, E, Koptelova, E, Leto, P, Ligustri, R, Lindfors, E, Lopez, J, Marscher, A, Mommert, M, Mujica, R, Nikolashvili, M, Nilsson, K, Palma, N, Pasanen, M, Roca-Sogorb, M, Ros, J, Roustazadeh, P, Sadun, A, Saino, J, Sigua, L, Sillanaa, A, Sorcia, M, Takalo, L, Tornikoski, M, Trigilio, C, Turchetti, R, Umana, G, Belloni, T, Blake, C, Bloom, J, Angelakis, E, Fumagalli, M, Hauser, M, Prochaska, J, Riquelme, D, Sievers, A, Starr, D, Tagliaferri, G, Ungerechts, H, Wagner, S, Zensus, J, Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)

Subjects
individual: 3C 66A [BL Lacertae objects], Ciencias Físicas, spectral energy-distribution, Astrophysics, BL Lacertae objects: individual (3C 66A), bright blazars, 01 natural sciences, law.invention, purl.org/becyt/ford/1 [https], bl lacertae objects, Astronomi, astrofysik och kosmologi, law, Astronomy, Astrophysics and Cosmology, 010303 astronomy & astrophysics, Physics, High Energy Astrophysical Phenomena (astro-ph.HE), radio-sources, [SDU.ASTR.HE]Sciences of the Universe [physics]/Astrophysics [astro-ph]/High Energy Astrophysical Phenomena [astro-ph.HE], epoch vlbi survey, 95.45.+i, 96.60.qe,95.55.Ka, Gamma ray, veritas observations, large-area telescope, Wavelength, Gamma rays: galaxie, active [galaxies], galaxies [gamma rays], Spectral energy distribution, BL Lacertae objects: individual: 3C 66A, Astrophysics - High Energy Astrophysical Phenomena, CIENCIAS NATURALES Y EXACTAS, BL Lac object, individual (3C 66A) [BL Lacertae objects], [PHYS.ASTR.HE]Physics [physics]/Astrophysics [astro-ph]/High Energy Astrophysical Phenomena [astro-ph.HE], Astrophysics::High Energy Astrophysical Phenomena, galaxies: active, FOS: Physical sciences, Telescope, 0103 physical sciences, gamma rays: galaxies, Blazar, tev blazars, 010308 nuclear & particles physics, Scattering, background-radiation, Astronomy and Astrophysics, purl.org/becyt/ford/1.3 [https], Astronomía, Space and Planetary Science, active galactic nuclei, ddc:520, Fermi Gamma-ray Space Telescope
Abstract

著者人数：328名, Accepted: 2010-10-29, 資料番号: SA1002650000

Published
2011
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12. Erratum: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (Nature Genetics (2010) 42 (105-116))

Author

Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Mägi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparsø, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, De Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jørgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martínez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orr, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigursson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvänen, A-C, Tanaka, T, Thorand, B, Tichet, J, Tönjes, A, Tuomi, T, Uitterlinden, AG, Van Dijk, KW, Van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Consortium, D, Consortium, G, Consortium, GB, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Ríos, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Hamsten, A, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, and Barroso, I

Published
2010

13. Salty brines on the Mediterranean sea floor

Author

WALLMANN, E. SUESS, G. H. WESTBROOK, G. WINCKLER, M. B. CITA AND THE MEDRIFF CONSORTIUM G. K. WESTBROOK, DELLA VEDOVA, BRUNO, Wallmann, E., Sue, G. H., Westbrook, G., Winckler, M. B. CITA AND THE MEDRIFF CONSORTIUM G. K., Westbrook, and DELLA VEDOVA, Bruno

Subjects
brine lakes, Mediterranean Ridge, Warm brine
Published
1997

14. Replication study and meta-analysis in European samples supports association of the 3p21.1 locus with bipolar disorder

Author

Vassos, E., Steinberg, S., Cichon, S., Breen, G., Sigurdsson, E., Andreassen, O.A., Djurovic, S., Morken, G., Grigoroiu-Serbanescu, M., Diaconu, C.C., Czerski, P.M., Hauser, J., Babadjanova, G., Abramova, L.I., Muhleisen, T.W., Nothen, Markus, Rietschel, M., McGuffin, P., St Clair, D., Gustafsson, O., Melle, I., Pietilainen, O.P., Ruggeri, M., Tosato, S., Werge, T., Ophoff, R.A., Consortium, G., Rujescu, D., Borglum, A.D., Mors, O., Mortensen, P.B., Demontis, D., Hollegaard, M.V., van Winkel, R., Kenis, G., De Hert, M., Rethelyi, J.M., Bitter, I., Rubino, I.A., Golimbet, V., Kiemeney, L.A., Berg, L.H. van den, Franke, B., Jonsson, E.G., Farmer, A., Stefansson, H., Stefansson, K., Collier, D.A., Vassos, E., Steinberg, S., Cichon, S., Breen, G., Sigurdsson, E., Andreassen, O.A., Djurovic, S., Morken, G., Grigoroiu-Serbanescu, M., Diaconu, C.C., Czerski, P.M., Hauser, J., Babadjanova, G., Abramova, L.I., Muhleisen, T.W., Nothen, Markus, Rietschel, M., McGuffin, P., St Clair, D., Gustafsson, O., Melle, I., Pietilainen, O.P., Ruggeri, M., Tosato, S., Werge, T., Ophoff, R.A., Consortium, G., Rujescu, D., Borglum, A.D., Mors, O., Mortensen, P.B., Demontis, D., Hollegaard, M.V., van Winkel, R., Kenis, G., De Hert, M., Rethelyi, J.M., Bitter, I., Rubino, I.A., Golimbet, V., Kiemeney, L.A., Berg, L.H. van den, Franke, B., Jonsson, E.G., Farmer, A., Stefansson, H., Stefansson, K., and Collier, D.A.

Abstract

Item does not contain fulltext, BACKGROUND: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including major depression and schizophrenia. METHODS: To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the PBRM1 gene. Results from the different case-control groups were combined with the inverse variance weighting method. RESULTS: In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 x 10(-9)). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, p = .21). CONCLUSIONS: There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder.

Published
2012

15. LAB-MOLECULAR EPIDEMIOLOGY

Author

Bie, L., primary, Zhao, G., additional, McClland, M., additional, Ju, Y., additional, Li, P. Y., additional, Zhou, D. J., additional, Jin, Z., additional, Bie, L., additional, Jenkins, R. B., additional, Xiao, Y., additional, Sicotte, H., additional, Decker, P. A., additional, Kollmeyer, T. M., additional, Hansen, H. M., additional, Kosel, M. L., additional, Zheng, S., additional, Walsh, K. M., additional, Rice, T., additional, Bracci, P., additional, Smirnov, I., additional, Patoka, J. F., additional, Hsuang, G., additional, Wiemels, J. L., additional, Tehan, T., additional, Pico, A. R., additional, Prados, M. D., additional, Berger, M. S., additional, Caron, A. A., additional, Fink, S. R., additional, Halder, C., additional, Rynearson, A. L., additional, Fridley, B. L., additional, O'Neill, B. P., additional, Giannini, C., additional, Lachance, D. H., additional, Wienke, J. K., additional, Eckel-Passow, J. E., additional, Wrensch, M. R., additional, Aref, D., additional, Perry, A., additional, Taylor, M., additional, Eberhardt, C., additional, Olson, J., additional, Moffatt, C., additional, Croul, S., additional, Maurice, C., additional, Belanger, K., additional, Berthelet, F., additional, Weng, X., additional, Amirian, E. S., additional, Liu, Y., additional, Okada, H., additional, Sarkar, S. N., additional, Bondy, M. L., additional, Scheurer, M. E., additional, Verhaak, R., additional, Sarkar, S., additional, Scheurer, M., additional, Bondy, M., additional, Melin, B., additional, Wang, Z., additional, Rajaraman, P., additional, Chanock, S., additional, Consortium, G., additional, Smith, A., additional, Accomando, W. P., additional, Houseman, E.-A., additional, Marsit, C. J., additional, Weincke, J. K., additional, and Kelsey, K. T., additional

Published
2012
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16. Variations of collagen-encoding genes are associated with exercise-induced muscle damage.

Author

Baumert, P., Consortium, G-REX, Stewart, E., Lake, M. J., Drust, B., and Erskine, R. M.

Subjects
*SKELETAL muscle, *MUSCLE strength, *MUSCLE contraction, *EXERCISE physiology, *SINGLE nucleotide polymorphisms
Abstract

We investigated whether single nucleotide polymorphisms (SNPs) within genes encoding the alpha-1 chain of type I (COL1A1, rs2249492; rs1800012), type II (COL2A1, rs2070739), and type V (COL5A1, rs12722) collagen were associated with the variable response to exercise-induced muscle damage (EIMD). Knee extensor muscle strength and soreness were assessed pre-, post-, and 48 h post-EIMD (120 maximal eccentric knee extensor contractions) in 65 young healthy participants, who were genotyped for the aforementioned SNPs. We found that COL1A1 (minor) T-allele carriers (rs1800012) and (major) T-allele homozygotes (rs2249492) were generally weaker (P = 0.019); and (minor) A-allele carriers of COL2A1 (P = 0.002) and (major) T-allele carriers of COL5A1 (P = 0.004) SNPs reported greater muscle soreness, all compared with their respective major (rs1800012; rs2070739) and minor (rs2249492; rs12722) allele homozygote counterparts. To conclude, the risk alleles of these four SNPs appear to negatively influence muscle strength and post-EIMD recovery, possibly via a dysregulated collagen network affecting the muscle's mechanical properties. [ABSTRACT FROM AUTHOR]

Published
2018
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19. Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion

Author

Brennecke, Nicholas, Cali, Ignazio, Mok, Tze, Speedy, Helen, Consortium, Genomics England Research, Hosszu, Laszlo, Stehmann, Christiane, Cracco, Laura, Puoti, Gianfranco, Prior, Thomas, Cohen, Mark, Collins, Steven, Mead, Simon, Appleby, Brian, Brennecke, N., Cali, I., Mok, T. H., Speedy, H., Consortium, G. E. R., Hosszu, L. L. P., Stehmann, C., Cracco, L., Puoti, G., Prior, T. W., Cohen, M. L., Collins, S. J., Mead, S., and Appleby, B. S.

Subjects
Male, Prions, animal diseases, Population, prion disease, Disease, Biology, octapeptide repeat insertion, Microbiology, Asymptomatic, Article, Creutzfeldt-Jakob Syndrome, Prion Proteins, Prion Diseases, Methionine, Genetic, National Prion Clinic, Virology, mental disorders, medicine, Humans, genetics, Allele, education, Alleles, Aged, Genetic testing, Aged, 80 and over, Genetics, education.field_of_study, medicine.diagnostic_test, Brain, Middle Aged, Penetrance, QR1-502, Creutzfeldt-Jakob disease, nervous system diseases, Mutagenesis, Insertional, Infectious Diseases, Female, genetic Creutzfeldt-Jakob disease, medicine.symptom, Oligopeptides, Asymptomatic carrier
Abstract

Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk.

Published
2021
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20. A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk

Author

Daniele Campa, Katja Butterbach, Susan L. Slager, Christine F. Skibola, Silvia de Sanjosé, Yolanda Benavente, Nikolaus Becker, Lenka Foretova, Marc Maynadie, Pierluigi Cocco, Anthony Staines, Rudolf Kaaks, Paolo Boffetta, Paul Brennan, Lucia Conde, Paige M. Bracci, Neil E. Caporaso, Sara S. Strom, Nicola J. Camp, James R. Cerhan, GEC Consortium, Federico Canzian, Alexandra Nieters, Campa, D., Butterbach, K., Slager, S.L., Skibola, C.F., De Sanjosé, S., Benavente, Y., Becker, N., Foretova, L., Maynadie, M., Cocco, P., Staines, A., Kaaks, R., Boffetta, P., Brennan, P., Conde, L., Bracci, P.M., Caporaso, N.E., Strom, S.S., Camp, N.J., Cerhan, J.R., Consortium, G., Canzian, F., and Nieters, A.

Subjects
Cytoplasmic And Nuclear Receptor, Technology, Cancer Research, Receptors, Steroid, Abcg2, Chronic lymphocytic leukemia, Gene, BCL9, Risk Factors, Xenobiotic, ATP Binding Cassette Transporter, Subfamily G, Member 2, Poison, multidrug resistance protein 2, Allele, Genetics, education.field_of_study, Pregnane X receptor, B-Cell Chronic Lymphocytic Leukemia, biology, Multidrug resistance-associated protein 2, pregnane x receptor, Multiple Drug Resistance, Multidrug Resistance-Associated Protein 2, Neoplasm Proteins, multidrug resistance 1, Oncology, breast cancer resistance protein, Multidrug Resistance-Associated Proteins, Case-Control Studie, Breast Neoplasm, B-Cell Lymphoma, ATP Binding Cassette Transporter, Subfamily B, ATP-Binding Cassette Transporter, Maintenance, Population, Single-nucleotide polymorphism, lymphoma, Polymorphism, Single Nucleotide, Article, medicine, Humans, Genetic Predisposition to Disease, ATP Binding Cassette Transporter, Subfamily B, Member 1, education, Regulator Gene, Hematologic Neoplasm, Proteins, medicine.disease, Haplotypes, Single Nucleotide Polymorphism, biology.protein, Neoplasm, ATP-Binding Cassette Transporters
Abstract

Owing to their role in controlling the efflux of toxic compounds, transporters are central players in the process of detoxification and elimination of xenobiotics, which in turn is related to cancer risk. Among these transporters, ATP-binding cassette B1/multidrug resistance 1 (ABCB1/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP) affect susceptibility to many hematopoietic malignancies. The maintenance of regulated expression of these transporters is governed through the activation of intracellular "xenosensors" like the nuclear receptor 1I2/pregnane X receptor (NR1I2/PXR). SNPs in genes encoding these regulators have also been implicated in the risk of several cancers. Using a tagging approach, we tested the hypothesis that common polymorphisms in the transporter genes ABCB1, ABCC2, ABCG2 and the regulator gene NR1I2 could be implicated in lymphoma risk. We selected 68 SNPs in the four genes, and we genotyped them in 1,481 lymphoma cases and 1,491 controls of the European case-control study (EpiLymph) using the Illumina GoldenGate® assay technology. Carriers of the SNP rs6857600 minor allele in ABCG2 was associated with a decrease in risk of B-cell lymphoma (B-NHL) overall (p < 0.001). Furthermore, a decreased risk of chronic lymphocytic leukemia (CLL) was associated with the ABCG2 rs2231142 variant (p = 0.0004), which could be replicated in an independent population. These results suggest a role for this gene in B-NHL susceptibility, especially for CLL. Copyright © 2011 UICC.

Published
2012

21. Regulation of protein abundance in normal human tissues.

Author

Fang H, Jiang L, da Veiga Leprevost F, Jian R, Chan J, Glinos D, Lappalainen T, Nesvizhskii AI, Reiner AP, Consortium G, Snyder MP, and Tang H

Abstract

We report a systematic quantification of 10,841 unique proteins from over 700 GTEx samples, representing five human tissues. Sex, age and genetic factors are associated with variation in protein abundance. In total, 1981 cis-protein quantitative trait loci (cis-pQTL) are identified, of which a majority of protein targets have not been assayed in the recent plasma-based proteogenomic studies. Integrating transcriptomic information from matching tissues delineates concordant as well as discordant expression patterns at RNA and protein levels. Juxtaposition of data from different tissues indicates both shared and tissue-specific genetic architecture that underlie protein abundance. Complementing genomic annotation, RNA-based eQTL studies, as well as the recent establishment of plasma-based proteogenomic characterization, tissue-pQTLs shed light on biology underlying genotype-phenotype association of complex traits and diseases.

Published
2025
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22. Phylogenomic evolutionary insights in the fern family Gleicheniaceae.

Author

Vieira Lima L, Salino A, Kessler M, Rouhan G, Testo WL, Suzart Argolo C, Consortium G, and Elias Almeida T

Subjects
Phylogeny, Biological Evolution, Genomics, Plastids genetics, Ferns
Abstract

The pantropical fern family Gleicheniaceae comprises approximately 157 species. Seven genera are currently recognized in the family, although their monophyly is still uncertain due to low sampling in phylogenetic studies. We examined the monophyly of the genera through extended sampling, using the first phylogenomic inference of the family including data from both nuclear and plastid genomes. Seventy-six samples were sequenced (70 Gleicheniaceae species and six outgroups) using high throughput sequencing, including all seven currently recognized genera. Plastid and nuclear data were recovered and assembled; the nuclear data was phased to reduce paralogy as well as hybrid noise in the final recovered topology. Maximum likelihood trees were built for each locus, and a concatenated dataset was built for both datasets. A species tree based on a multispecies coalescent model was generated, and divergence time analyses performed. We here present the first genomic phylogenetic inferences concerning Gleicheniaceae, confirming the monophyly of most genera except Sticherus, which we recovered as paraphyletic. Although most of the extant genera of Gleicheniaceae originated during the Mesozoic, several genera show Neogene and even Quaternary diversifications, and our results suggest that reticulation and polyploidy may have played significant roles during this diversification. However, some genera, such as Rouxopteris and Stromatopteris, appear to represent evolutionary relicts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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23. Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup.

Author

Vergote I, Gonzalez-Martin A, Lorusso D, Gourley C, Mirza MR, Kurtz JE, Okamoto A, Moore K, Kridelka F, McNeish I, Reuss A, Votan B, du Bois A, Mahner S, Ray-Coquard I, Kohn EC, Berek JS, Tan DSP, Colombo N, Zang R, Concin N, O'Donnell D, Rauh-Hain A, Herrington CS, Marth C, Poveda A, Fujiwara K, Stuart GCE, Oza AM, and Bookman MA

Subjects
Carcinoma, Ovarian Epithelial, Consensus, Female, Forecasting, Humans, Ovarian Neoplasms therapy
Abstract

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer., Competing Interests: Declaration of interests IV reports grants from Amgen and Roche for corporate-sponsored research; payment (institutional) for contracted research from Oncoinvent and Genmab; consulting fees (institutional) from Amgen (Europe), AstraZeneca, Clovis Oncology, Carrick Therapeutics, Deciphera Pharmaceuticals, Elevar Therapeutics, F Hoffmann-La Roche, Genmab, GlaxoSmithKline, Immunogen, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Octimet Oncology, Oncoinvent, Sotio, Verastem Oncology, and Zentalis; consulting fees from Deciphera Pharmaceuticals, Jazzpharma, Oncoinvent; honoraria from Agenus, Aksebio, AstraZeneca, Bristol Myers Squibb (BMS), Deciphera Pharmaceuticals, Eisai, F Hoffmann-La Roche, Genmab, GlaxoSmithKline, Immunogen, Jazzpharma, Karyopharm, MSD, Novocure, Novartis, Oncoinvent, Seagen, and Sotio; participation on a data safety monitoring board or advisory board for Agenus, AstraZeneca, BMS, Deciphera Pharmaceuticals, Eisai, F Hoffmann-La Roche, Genmab, GlaxoSmithKline, Immunogen, MSD, Novocure, Novartis, Seagen, and Sotio; and travel support from Amgen, MSD, Tesaro, AstraZeneca, and Roche. AG-M reports grants from Tesaro/GlaxoSmithKline, and Roche (funding for IST trial); consulting fees from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GlaxoSmithKline, ImmunoGen, Merck Sharp & Dohme, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Sotio, and Sutro; honoraria from AstraZeneca, PharmaMar, Roche, GlaxoSmithKline, and Clovis; meeting or travel support from AstraZeneca, Pharmamar Roche, and Tesaro; participation on a data safety monitoring board or advisory board for Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GlaxoSmithKline, ImmunoGen, Merck Sharp & Dohme, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Sotio, and Sutro; is a member of GEICO; and was Chair of the European Network for Gynaecological Oncological Trials (ENGOT; 2018–20). DL reports grants from GlaxoSmithKline, MSD, and Clovis Oncology; consulting fees from Pharmamar and Merck Serono; honoraria from GlaxoSmithKline, Clovis Oncology, AstraZeneca, and MSD; payment for expert testimony from Clovis Oncology; meeting or travel support from GlaxoSmithKline, Roche, and Pharmamar; participation on a data safety monitoring board or advisory board for Novartis, Seagen, MSD, AstraZeneca, Immunogen, Genmab, Amgen, Clovis Oncology, GlaxoSmithKline, and Merck Serono; and is Chair of the Gynecological Cancer Accademy and on the board of directors of the GCIG. CG reports grants (institutional) for preclinical, clinical, or translational research from AstraZeneca, Novartis, GlaxoSmithKline, Tesaro, Clovis, MSD, BergenBio, Aprea, Nucana, and Medannexin; consulting fees from AstraZeneca, MSD, GlaxoSmithKline, and Tesaro; honoraria for lectures or presentations from AstraZeneca, MSD, GlaxoSmithKline, Tesaro, Clovis, Roche, Nucana, Chugai, Takeda, and Cor2Ed (preparation of educational material); advisory board attendance for AstraZeneca, MSD, GlaxoSmithKline, Tesaro, Roche, Nucana, and Chugai; and is a committee member of the Scottish Medicines Consortium. MRM reports research grants from AstraZeneca, Ultimovacs, Apexigen, and GlaxoSmithKline; honoraria as invited speaker for AstraZeneca and GlaxoSmithKline; participation on advisory boards for AstraZeneca, GlaxoSmithKline, Karyopharm, Nuvation Bio, Roche, Zailab, Merck, Biocad, and Boehringer Ingelheim; is a member of the board of directors for Karyopharm and Sera Prognostics; owns stocks or shares in Karyopharm and Sera Prognostics; and is Study Chair (institutional) for Deciphara and Mersana. J-EK reports honoraria from Clovis; meeting or travel support from AstraZeneca and GlaxoSmithKline; and participation on a data safety monitoring board or advisory board for AstraZeneca and GlaxoSmithKline. AO reports grants (institutional) from Kaken, Chugai, Tsumura & Co, Daiichi Sankyo, Shinnihonseiyaku, Mochida, CMIC Holdings, ASKA, Takeda, Pfizer, AstraZeneca, Terumo, MSD, Fuji Pharma, Kissei, Meiji Holdings, Taiho, Nippon Shinyaku, Linical, and Gyne Mom; and honoraria from Takeda, AstraZeneca, Zeria, MSD, Chugai, Kaken, and Eisai. KM reports consulting fees from Aravive, AstraZeneca, Alkemeres, Blueprint Pharma, Elevar, Eisai/Serono, GlaxoSmithKline/Tesaro, Genentech/Roche, Immunogen, IMab, Lilly, Mereo, Merck, Mersana, Myriad, OncXerna, Onconova, Tarveda, and VBL Therapeutics; honoraria from AstraZeneca, PTC Therapeutics, OncLive, Research to Practice, and Medscape; participation on a data safety monitoring board or advisory board for Incyte and SQZ Biotech; and is the Gynecologic Oncology Group Partners Associate Director and NRG (NSABP, RTOG and GOG) Ovarian Cancer Subcommittee Chair. FK reports consulting fees and honoraria from AstraZeneca, Pharmamar, Roche, Lilly, and Merck; participation on a data safety monitoring board or advisory board for AstraZeneca and Pharmamar; and is a BGOG steering committee member. IM reports honoraria from GlaxoSmithKline and AstraZeneca; participation on an advisory board for Clovis Oncology, AstraZeneca, and GlaxoSmithKline/Tesaro; and is part of the data monitoring committee for Transgene. AdB reports honoraria from AstraZeneca, Zodiac, GlaxoSmithKline/Tesaro, Clovis, Amgen, and MSD; participation on a data safety monitoring board or advisory board for AstraZeneca, Roche, GlaxoSmithKline/Tesaro, Clovis, Amgen, GenMab, and MSD; and is a member of the AGO Study Group and ENGOT. SM reports grants (institutional), consulting fees (institutional), honoraria (institutional), and meeting or travel support from AbbVie, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Medac, MSD, Novartis, Olympus, PharmaMar, Pfizer, Roche, Sensor Kinesis, Teva, and Tesaro. IR-C reports honoraria from Amgen, AstraZeneca, BMS, Clovis Oncology, Genmab, GlaxoSmithKline, ImmunoGen, Merck Sharp & Dohme, Novartis, Pfizer/Merck-Sereno, Deciphera, Mersana, Agenus, PharmaMar, and Roche; meeting and travel support from Roche, AstraZeneca, GlaxoSmithKline, Clovis, and MSD; and is President of the GINECO group. JSB reports research grants from Immunogen and Tesaro; and participation on a data safety monitoring board or advisory board for ENGOT (MK-7339-001 ENGOT-ov43 Safety DMC MK-3475 B96 DMC) and OncoQuest. DSPT reports grants or contracts (institutional) from National Medical Research Council Singapore, Karyopharm Therapeutics, Pangestu Family Foundation Gynaecological Cancer Research Fund, BMS, AstraZeneca, Roche, Bayer; consulting fees from AstraZeneca, Bayer, Eisai, Merck Serono, GlaxoSmithKline, Genentech/Roche, MSD, and Genmab; honoraria from AstraZeneca, GlaxoSmithKline, Roche, Eisai, MSD, Merck Serono; is the President of GCGS and APGOT Chair; and has stock or stock options in Asian Microbiome Library. NCol reports provision of study materials (personal); consulting fees (personal) from Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GlaxoSmithKline, Tesaro, Pfizer, BIOCAD, Immunogen, Mersana, Eisai, and Oncxerna; and honoraria (personal) from AstraZeneca, Tesaro, Novartis, Clovis, MSD, GlaxoSmithKline, and Eisai. NCon reports consulting fees from Seagen, Akesobio, Ensai, GlaxoSmithKline, AstraZeneca, Mersana, Seattle Genetics, and eTheRNA Immunotherapies; honoraria from GlaxoSmithKline, Mersana, MSD, Medscape Oncology, AstraZeneca, and TouchIME; meeting and travel support from Roche, Genmab, and Amgen; participation on a data safety monitoring board or advisory board for Seagen, Akesobio, Ensai, GlaxoSmithKline, AstraZeneca, Mersana, Seattle Genetics, and eTheRNA Immunotherapies; and is President of the European Society of Gynaecological Oncology and Co-Chair of the ENGOT Early Drug Development Network. AR-H reports support for the present manuscript and grants from the US National Institutes of Health National Cancer Institute (K08 CA234333). CM reports consulting fees from Roche, Novartis, Amgen, MSD, AstraZeneca, Pfizer, Pharmamar, Curelean, Vertex, Tesaro, GlaxoSmithKline, and Seagen; honoraria from Roche, Novartis, Amgen, MSD, Pharmamar, AstraZeneca, Tesaro, GlaxoSmithKline, and Seagen; meeting or travel support from Roche and AstraZeneca; and participation on data safety monitoring board or advisory board for Roche, Novartis, Amgen, MSD, AstraZeneca, Pfizer, Pharmamar, Cerulean, Vertex, Tesaro, GlaxoSmithKline, and Seagen. AP reports participation on an advisory board (personal payment) from AstraZeneca and GlaxoSmithKline. KF reports participation on a data safety monitoring board or advisory board for Merck (ENGOT-en11/MK-3475-B21/GOG-3053); and is a member of GenomeBC. GCES reports participation on a data safety monitoring board or advisory board for Merck (ENGOT-en11/MK-3475-B21/GOG-3053); and is a member of GenomeBC. AMO is Chair or GCIG (unpaid) and Chief Executive Officer of Ozmosis Research (unpaid). MAB reports participation on a data safety monitoring board or advisory board (institutional) for Aravive (protocol steering committee), Immunogen, Genentech, Merck, and Sharp & Dohme. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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24. Mortality attributable to COVID-19 in nursing home residents: a retrospective study.

Author

Veronese N, Koyanagi A, Stangherlin V, Mantoan P, Chiavalin M, Tudor F, Pozzobon G, Tessarin M, and Pilotto A

Subjects
Aged, Aged, 80 and over, Female, Humans, Italy, Mortality, Nursing Homes, Prognosis, Retrospective Studies, SARS-CoV-2, COVID-19, Geriatric Assessment
Abstract

Aim: Coronavirus-19 disease (COVID-19) is a widespread condition in nursing home (NH). It is not known whether COVID-19 is associated with a higher risk of death than residents without COVID-19. Therefore, the aim of this study was to assess whether COVID-19 is associated with a higher mortality rate in NH residents, considering frailty status assessed with the Multidimensional Prognostic Index (MPI)., Methods: In this retrospective study, made in 31 NHs in Venice, Italy, the presence of COVID-19 was ascertained with a nasopharyngeal swab. Frailty was evaluated using the MPI, modified according to the tools commonly used in our NHs. A Cox's regression analysis was used reporting the results as hazard ratios (HRs) with 95% confidence intervals (CIs), using COVID-19 as exposure and mortality as outcome and stratified by MPI tertiles. Similar analyses were run using MPI tertiles as exposure., Results: Overall, 3946 NH residents (median age = 87 years, females: 73.9%) were eligible, with 1136 COVID-19 + . During a median follow-up of 275 days, higher values of MPI, indicating frailer people, were associated with an increased risk of mortality. The incidence of mortality in COVID-19 + was more than doubled than COVID-19- either in MPI-1, MPI-2 and MPI-3 groups. The presence of COVID-19 increased the risk of death (HR = 1.85; 95% CI 1.59-2.15), also in the propensity score model using MPI as confounder (HR = 2.48; 95% CI 2.10-2.93)., Conclusion: In this retrospective study of NH residents, COVID-19 was associated with a higher risk of all-cause mortality than those not affected by COVID-19 also considering the different grades of frailty.

Published
2021
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25. Complex epilepsy: it's all in the history.

Author

Silvennoinen K, Martins Custodio H, Balestrini S, Rugg-Gunn F, England Research Consortium G, and Sisodiya SM

Abstract

Competing Interests: Competing interests: SMS reports representing the Association of British Neurologists and The Royal College of Physicians (London) at the MHRA Valproate Stakeholders Network, is a member of the scientific advisory board of Dravet Syndrome UK, patron of AHC UK, and has received honoraria or grant funding from UCB, Eisai, Vitaflo and Nutricia. SB has received honoraria from UCB. KS and HMC declare no potential competing interests. FR-G is a committee member of the MHRA Neurology, Pain and Psychiatry Expert Advisory Group and MHRA Sodium Valproate Expert Working Group, and council member of ILAE British branch and has received honoraria from LivaNova.

Published
2020
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26. PhenomeXcan: Mapping the genome to the phenome through the transcriptome.

Author

Pividori M, Rajagopal PS, Barbeira A, Liang Y, Melia O, Bastarache L, Park Y, Consortium G, Wen X, and Im HK

Abstract

Large-scale genomic and transcriptomic initiatives offer unprecedented insight into complex traits, but clinical translation remains limited by variant-level associations without biological context and lack of analytic resources. Our resource, PhenomeXcan, synthesizes 8.87 million variants from genome-wide association study summary statistics on 4091 traits with transcriptomic data from 49 tissues in Genotype-Tissue Expression v8 into a gene-based, queryable platform including 22,515 genes. We developed a novel Bayesian colocalization method, fast enrichment estimation aided colocalization analysis (fastENLOC), to prioritize likely causal gene-trait associations. We successfully replicate associations from the phenome-wide association studies (PheWAS) catalog Online Mendelian Inheritance in Man, and an evidence-based curated gene list. Using PhenomeXcan results, we provide examples of novel and underreported genome-to-phenome associations, complex gene-trait clusters, shared causal genes between common and rare diseases via further integration of PhenomeXcan with ClinVar, and potential therapeutic targets. PhenomeXcan (phenomexcan.org) provides broad, user-friendly access to complex data for translational researchers., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Published
2020
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28. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions.

Author

Karam A, Ledermann JA, Kim JW, Sehouli J, Lu K, Gourley C, Katsumata N, Burger RA, Nam BH, Bacon M, Ng C, Pfisterer J, Bekkers RLM, Casado Herráez A, Redondo A, Fujiwara H, Gleeson N, Rosengarten O, Scambia G, Zhu J, Okamoto A, Stuart G, and Ochiai K

Subjects
Carcinoma, Ovarian Epithelial, Female, Humans, Neoplasms, Glandular and Epithelial therapy, Ovarian Neoplasms therapy, Research Design
Abstract

The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others. (ii) Control arms for chemotherapy: for advanced stage ovarian cancer the standard is intravenous 3-weekly carboplatin and paclitaxel. Acceptable alternatives, which should be stratified variables in trials when more than one regimen is offered, include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal therapy. (iii) Trial Endpoints: overall survival is the preferred primary endpoint for first-line clinical trials with or without a maintenance component. Progression-free survival (PFS) is an alternative primary endpoint, but if PFS is chosen overall survival must be measured as a secondary endpoint and PFS must be supported by additional endpoints, including predefined patient reported outcomes and time to first or second subsequent therapy. For neoadjuvant therapy, additional 'window of opportunity' endpoints should be included., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2017
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