Author: "Balschun, T" - Searchworks@Jio Institute Digital Library Search Results

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37 results on '"Balschun, T"'

1. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants

Author: Juran BD, Hirschfield GM, Invernizzi P, Atkinson EJ, Li Y, Xie G, Kosoy R, Ransom M, Sun Y, Bianchi I, Schlicht EM, Lleo A, Coltescu C, Bernuzzi F, Podda M, Lammert C, Shigeta R, Chan LL, Balschun T, Marconi M, Cusi D, Heathcote EJ, Mason AL, Myers RP, Milkiewicz P, Odin JA, Luketic VA, Bacon BR, Bodenheimer HC Jr, Liakina V, Vincent C, Levy C, Franke A, Gregersen PK, Bossa F, Gershwin ME, deAndrade M, Amos CI, Italian PBC Genetics Study Group, Lazaridis KN, Seldin MF, Siminovitch KA, Almasio PL, Alvaro D, Andriulli A, Barlassina C, Battezzati PM, Benedetti A, Bragazzi M, Brunetto M, Bruno S, Caliari L, Casella G, Civardi F, Coco B, Colli A, Colombo M, Colombo S, Cursaro C, Crocè LS, Crosignani A, Donato F, Fabris L, Ferrari C, Floreani A, Fontana R, Galli A, Grattagliano I, Lazzari R, Macaluso F, Malinverno F, Marra F, Marzioni M, Mascia E, Mattalia A, Montanari R, Morini L, Morisco F, Niro GA, Picciotto A, Portincasa P, Prati D, Rosina F, Rossi S, Selmi C, Spinzi G, Strazzabosco M, Tarallo S, Tiribelli C, Toniutto P, Vinci M, Zuin M., ANDREONE, PIETRO, MURATORI, LUIGI, MURATORI, PAOLO, Juran BD, Hirschfield GM, Invernizzi P, Atkinson EJ, Li Y, Xie G, Kosoy R, Ransom M, Sun Y, Bianchi I, Schlicht EM, Lleo A, Coltescu C, Bernuzzi F, Podda M, Lammert C, Shigeta R, Chan LL, Balschun T, Marconi M, Cusi D, Heathcote EJ, Mason AL, Myers RP, Milkiewicz P, Odin JA, Luketic VA, Bacon BR, Bodenheimer HC Jr, Liakina V, Vincent C, Levy C, Franke A, Gregersen PK, Bossa F, Gershwin ME, deAndrade M, Amos CI, Italian PBC Genetics Study Group, Lazaridis KN, Seldin MF, Siminovitch KA, Almasio PL, Alvaro D, Andreone P, Andriulli A, Barlassina C, Battezzati PM, Benedetti A, Bragazzi M, Brunetto M, Bruno S, Caliari L, Casella G, Civardi F, Coco B, Colli A, Colombo M, Colombo S, Cursaro C, Crocè LS, Crosignani A, Donato F, Fabris L, Ferrari C, Floreani A, Fontana R, Galli A, Grattagliano I, Lazzari R, Macaluso F, Malinverno F, Marra F, Marzioni M, Mascia E, Mattalia A, Montanari R, Morini L, Morisco F, Muratori L, Muratori P, Niro GA, Picciotto A, Portincasa P, Prati D, Rosina F, Rossi S, Selmi C, Spinzi G, Strazzabosco M, Tarallo S, Tiribelli C, Toniutto P, Vinci M, Zuin M., Juran, Bd, Hirschfield, Gm, Invernizzi, P, Atkinson, Ej, Li, Y, Xie, G, Kosoy, R, Ransom, M, Sun, Y, Bianchi, I, Schlicht, Em, Lleo, A, Coltescu, C, Bernuzzi, F, Podda, M, Lammert, C, Shigeta, R, Chan, Ll, Balschun, T, Marconi, M, Cusi, D, Heathcote, Ej, Mason, Al, Myers, Rp, Milkiewicz, P, Odin, Ja, Luketic, Va, Bacon, Br, Bodenheimer HC, Jr, Liakina, V, Vincent, C, Levy, C, Franke, A, Gregersen, Pk, Bossa, F, Gershwin, Me, Deandrade, M, Amos, Ci, Lazaridis, Kn, Seldin, Mf, Siminovitch, Ka, Morisco, Filomena, Italian PBC Genetics Study, Group, Juran, B, Hirschfield, G, Atkinson, E, Schlicht, E, Chan, L, Heathcote, E, Mason, A, Myers, R, Odin, J, Luketic, V, Bacon, B, Bodenheimer, H, Gregersen, P, Gershwin, M, Amos, C, Italian PBC Genetics Study, G, Lazaridis, K, Seldin, M, Siminovitch, K, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Civardi, F, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, L, Crosignani, A, Donato, F, Fabris, L, Ferrari, C, Floreani, A, Fontana, R, Galli, A, Grattagliano, I, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mascia, E, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, Picciotto, A, Portincasa, P, Prati, D, Rosina, F, Rossi, S, Selmi, C, Spinzi, G, Strazzabosco, M, Tarallo, S, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Almasio, Pl, Battezzati, Pm, Croce', Saveria, Niro, Ga, Tiribelli, Claudio, and Zuin, M.
Subjects: MULTILOCUS GENOTYPE DATA, PRIMARY BILIARY CIRRHOSIS, PBC, 0302 clinical medicine, Gene Frequency, MED/12 - GASTROENTEROLOGIA, HLA Antigens, REGULATORY T-CELLS, RHEUMATOID-ARTHRITIS, VITAMIN-D, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Genetics, CLASSICAL HLA ALLELES, 0303 health sciences, Liver Cirrhosis, Biliary, PBC, HLA alleles, Association Studies Articles, CELIAC-DISEASE, General Medicine, GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY LOCI, GENETIC RISK, 3. Good health, Chromosomes, Human, Pair 1, SINGLE NUCLEOTIDE POLYMORPHISMS, 030211 gastroenterology & hepatology, Chromosomes, Human, Pair 7, GENETIC ANALYSES, Genotype, Single-nucleotide polymorphism, Locus (genetics), Human leukocyte antigen, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Humans, SNP, Genetic Predisposition to Disease, Allele, Molecular Biology, Allele frequency, Alleles, 030304 developmental biology, Chromosomes, Human, Pair 13, Haplotype, Epistasis, Genetic, Genetic Loci, Case-Control Studies, Imputation (genetics)
Abstract: To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.
Published: 2012

2. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Author: Cordell, HJ, Han, Y, Mells, GF, Li, Y, Hirschfield, GM, Greene, CS, Xie, G, Juran, BD, Zhu, D, Qian, DC, Floyd, JAB, Morley, KI, Prati, D, Lleo, A, Cusi, D, Gershwin, ME, Anderson, CA, Lazaridis, KN, Invernizzi, P, Seldin, MF, Sandford, RN, Amos, CI, Siminovitch, KA, Schlicht, EM, Lammert, C, Atkinson, EJ, Chan, LL, De Andrade, M, Balschun, T, Mason, AL, Myers, RP, Zhang, J, Milkiewicz, P, Qu, J, Odin, JA, Luketic, VA, Bacon, BR, Bodenheimer, HC, Liakina, V, Vincent, C, Levy, C, Gregersen, PK, Almasio, PL, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, PM, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, MC, Brunetto, M, Bruno, S, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, LS, Crosignani, A, Donato, MF, Elia, G, Fabris, L, Ferrari, C, Floreani, A, Foglieni, B, Fontana, R, Galli, A, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Mousa Hani, S, Muratori, L, Muratori, P, Niro, GA, Palmieri, VO, Picciotto, A, Podda, M, Portincasa, P, Ronca, V, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, and Spreafico, M
Subjects: MD Multidisciplinary
Abstract: © 2015 Macmillan Publishers Limited. All rights reserved.Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined
Published: 2015

3. High-density mapping of the MHC identifies a shared role for HLA-DRB1∗01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis

Author: Goyette, P, Boucher, G, Mallon, D, Ellinghaus, E, Jostins, L, Huang, H, Ripke, S, Gusareva, ES, Annese, V, Hauser, SL, Oksenberg, JR, Thomsen, I, Leslie, S, Daly, MJ, Van Steen, K, Duerr, RH, Barrett, JC, McGovern, DPB, Schumm, LP, Traherne, JA, Carrington, MN, Kosmoliaptsis, V, Karlsen, TH, Franke, A, Rioux, JD, Abraham, C, Achkar, JP, Ahmad, T, Amininejad, L, Ananthakrishnan, AN, Andersen, V, Anderson, CA, Andrews, JM, Aumais, G, Baidoo, L, Baldassano, RN, Balschun, T, Bampton, PA, Barclay, M, Bayless, TM, Bethge, J, Bis, JC, Bitton, A, Brand, S, Brant, SR, Buning, C, Chew, A, Cho, JH, Cleynen, I, Cohain, A, Croft, A, D'Amato, M, Danese, S, De Jong, D, De Vos, M, Denapiene, G, Denson, LA, Devaney, KL, Dewit, O, D'Inca, R, Dubinsky, M, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, LR, Festen, EA, Fleshner, P, Florin, T, Franchimont, D, Fransen, K, Gearry, R, Georges, M, Gieger, C, and Glas, J
Subjects: digestive system diseases
Abstract: © 2015 Nature America, Inc. All rights reserved. Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1∗01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
Published: 2015

4. Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis

Author: Beaudoin, Melissa, Goyette, Philippe, Goel, Gautam, Louis, E., Mansfield, J. C., Mathew, C. G., McGovern, D. P., Mitrovic, M., Montgomery, G. W., Mowat, C., Newman, W., Palmieri, O., Panés, J., Lagace, Caroline, Parkes, M., Phillips, A., Ponsioen, C. Y., Potocnik, U., Prescott, N. J., Proctor, D. D., Radford-Smith, G. L., Regueiro, M., Rioux, J. D., Roberts, R., Annese, Vito, Rotter, J. I., Rutgeerts, P., Sanderson, J., Sans, M., Satsangi, J., Schreiber, S., Schumm, P., Seibold, F., Sharma, Y., Silverberg, M. S., Bitton, Alain, Simms, L. A., Steinhart, A., Targan, S. R., Taylor, K. D., Torkvist, L., Vermeire, S., Halfvarson, J., Verspaget, H. W., De Vos, M., Walters, T., Begun, Jakob, Wang, K., Weersma, R. K., Whiteman, D., Wijmenga, C., Brant, Steven R., Bresso, Francesca, Cho, Judy H., Duerr, Richard H., Halfvarson, Jonas, Boucher, Gabrielle, McGovern, Dermot P. B., Radford-Smith, Graham, Schreiber, Stefan, Schumm, Philip L., Sharma, Yashoda, Silverberg, Mark S., Weersma, Rinse K., Quebec IBD Genetics Consortium, NIDDK IBD Genetics Consortium, International IBD Genetics Consortium (IIBDGC), Lo, Ken Sin, D'Amato, Mauro, Vermeire, Severine, Franke, Andre, Lettre, Guillaume, Xavier, Ramnik J., Daly, Mark J., Rioux, John D., Aumais, G., Bernard, E. J., Bitton, A., Rivas, Manuel A., Cohen, A., Deslandres, C., Lahaie, R., Paré, P., Brant, S. R., Cho, J. H., Duerr, R. H., Stevens, Christine, Ahmad, T., Anderson, C. A., Annese, V., Baldassano, R. N., Balschun, T., Barclay, M., Barrett, J. C., Bayless, T. M., Bis, J. C., Alikashani, Azadeh, Brand, S., Bumpstead, S., Buning, C., Colombel, J. F., Cottone, M., D'Amato, M., D'Inca, R., Ladouceur, Martin, Daly, M. J., Denson, T., Dubinsky, M., Edwards, C., Ellinghaus, D., Florin, T., Franchimont, D., Franke, A., Gearry, R., Ellinghaus, David, Georges, M., Glas, J., Van Gossum, A., Griffiths, A. M., Guthery, S. L., Hakonarson, H., Haritunians, T., Hugot, J. P., de Jong, D. J., Jostins, L., Torkvist, Leif, Kugathasan, S., Kullak-Ublick, G., Latiano, A., Laukens, D., Lawrance, I., Lee, J., Lees, C. W., Lemann, M., Levine, A., Libioulle, C., and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Cancer Research, Génétique clinique, LIVER, Genome-wide association study, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, GENETIC-VARIANTS, Medicine and Health Sciences, Ethnicity, UBIQUITIN LIGASES, Genetics(clinical), Genetics (clinical), Genetics, 0303 health sciences, Ecology, High-Throughput Nucleotide Sequencing, CROHN-DISEASE, CROHNS-DISEASE, 3. Good health, 030220 oncology & carcinogenesis, Medical genetics, Biologie, Research Article, EXPRESSION, medicine.medical_specialty, Canada, lcsh:QH426-470, SUSCEPTIBILITY LOCI, Evolution, Ubiquitin-Protein Ligases, Ethnic Groups, Evolution des espèces, Biology, Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2], Polymorphism, Single Nucleotide, 03 medical and health sciences, Behavior and Systematics, medicine, Humans, Genetic Predisposition to Disease, Ligase activity, MODULATION, Allele, GENOME-WIDE ASSOCIATION, Molecular Biology, Genotyping, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, Ecologie, Biologie moléculaire, Receptors, Interleukin, medicine.disease, NUCLEAR FACTOR 4-ALPHA, Genetic architecture, Cancérologie, CARD Signaling Adaptor Proteins, lcsh:Genetics, CELLS, Colitis, Ulcerative, INTESTINAL EPITHELIAL-CELLS, Genome-Wide Association Study, INFLAMMATORY-BOWEL-DISEASE
Abstract: Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (~14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. © 2013 Beaudoin et al., 0, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2013

5. Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry

Author: Hunt, K.A., Smyth, D.J., Balschun, T., Ban, M., Mistry, V., Ahmad, T., Anand, V., Barrett, J.C., Bhaw-Rosun, L., Bockett, N.A., Brand, O.J., Brouwer, E., Concannon, P., Cooper, J.D., Dias, K.R.M., Diemen, C.C. van, Dubois, P.C., Edkins, S., Folster-Holst, R., Fransen, K., Glass, D.N., Heap, G.A.R., Hofmann, S., Huizinga, T.W.J., Hunt, S., Langford, C., Lee, J., Mansfield, J., Marrosu, M.G., Mathew, C.G., Mein, C.A., Muller-Quernheim, J., Nutland, S., Onengut-Gumuscu, S., Ouwehand, W., Pearce, K., Prescott, N.J., Posthumus, M.D., Potter, S., Rosati, G., Sambrook, J., Satsangi, J., Schreiber, S., Shtir, C., Simmonds, M.J., Sudman, M., Thompson, S.D., Toes, R., Trynka, G., Vyse, T.J., Walker, N.M., Weidinger, S., Zhernakova, A., Zoledziewska, M., Weersma, R.K., Gough, S.C.L., Sawcer, S., Wijmenga, C., Parkes, M., Cucca, F., Franke, A., Deloukas, P., Rich, S.S., Todd, J.A., Heel, D.A. van, Type 1 Diabet Genetics, UK Inflammatory Bowel Dis IBD, and Wellcome Trust Case
Published: 2012

6. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1,2q22.3 and 17q21.32

Author: Steffens, M., Leu, C., Ruppert, A., Zara, F., Striano, P., Robbiano, A., Capovilla, G., Tinuper, P., Gambardella, A., Bianchi, A., La neve, A., Crichiutti, G., de kovel, C. G., Trenité, D. K. -N., de haan, G., Lindhout, D., Gaus, V., Schmitz, B., Janz, D., Weber, Y. G., Becker, F., Lerche, H., Steinhoff, B. J., Kleefuß-Lie, A. A., Kunz, W. S., Surges, R., Elger, C. E., Muhle, H., Von spiczak, S., Ostertag, P., Helbig, I., Stephani, U., Møller, R. S., Hjalgrim, H., Dibbens, L. M., Bellows, S., Oliver, K., Mullen, S., Scheffer, I. E., Berkovic, S. F., Everett, K. V., Gardiner, M. R., Marini, Chiara, Guerrini, R., Lehesjoki, A., Siren, A., Guipponi, M., Malafosse, A., Thomas, P., Nabbout, R., Baulac, S., Leguern, E., Guerrero, R., Serratosa, J. M., Reif, P. S., Rosenow, F., Mörzinger, M., Feucht, M., Zimprich, F., Kapser, C., Schankin, C. J., Suls, A., Smets, K., De jonghe, P., Jordanova, A., Caglayan, H., Yapici, Z., Yalcin, D. A., Baykan, B., Bebek, N., Ozbek, U., Gieger, C., Wichmann, H., Balschun, T., Ellinghaus, D., Franke, A., Meesters, C., Becker, T., Wienker, T. F., Hempelmann, A., Schulz, H., Rüschendorf, F., Leber, M., Pauck, S. M., Trucks, H., Toliat, M. R., Nürnberg, P., Avanzini, G., Koeleman, B. P., Sander, T., Weckhuysen, S., Claes, L., Deprez, L., Van Dyck, T., Deconinck, T., De Jonghe, P., Velizarova, R., Dimova, P., Radionova, M., Tournev, I., Kancheva, D., Kaneva, R., Lehesjoki, A. -E., von Spiczak, S., Martin Klein, K., Oertel, W. H., Hamer, H. M., Marini, C., Mei, D., Norci, V., Pezzella, M., La Neve, A., Vigliano, P., Vanadia, F., Vignoli, A., Coppola, A., Striano, S., Egeo, G., Teresa Giallonardo, M., Franceschetti, S., Belcastro, V., Benna, P., Coppola, G., De Palo, A., Ferlazzo, E., Vecchi, M., Martinelli, V., Bisulli, F., Beccaria, F., Del Giudice, E., Mancardi, M., Stranci, G., Scabar, A., Gobbi, G., Giordano, I., de Haan, G. -J., Giraldez, B. G., Ozbeck, U., Ozdemir, O., Ugur, S., Kocasoy-Orhan, E., Yücesan, E., Cine, N., Gokyigit, A., Gurses, C., Gul, G., Ozkara, C., Yalcin, O., Turkdogan, D., Dizdarer, G., Agan, K., Steffens, Michael, Leu, Costin, Ruppert, Ann-Kathrin, Zara, Frederico, Dibbens, Leanne Michelle, Sander, Thomas, EPICURE Consortium, Epicure, Consortium, DEL GIUDICE, Ennio, Steffens, M, Leu, C, Ruppert, Ak, Zara, F, Striano, P, Robbiano, A., Coppola, Antonietta, E. P. I. C. U. R. E. Consortium, E. M. I.Net Consortium, M. Steffen, C. Leu, A. Ruppert, F. Zara, P. Striano, A. Robbiano, G. Capovilla, P. Tinuper, A. Gambardella, A. Bianchi, A. L. Neve, G. Crichiutti, C. G. F, D. K. Trenité, G. d. Haan, D. Lindhout, V. Gau, B. Schmitz, D. Janz, Y. G. Weber, F. Becker, H. Lerche, B. J. Steinhoff, A. A. Kleefuß-Lie, W. S. Kunz, R. Surge, C. E. Elger, H. Muhle, S. v. Spiczak, P. Ostertag, I. Helbig, U. Stephani, R. S. Møller, H. Hjalgrim, L. M. Dibben, S. Bellow, K. Oliver, S. Mullen, I. E. Scheffer, S. F. Berkovic, K. V. Everett, M. R. Gardiner, C. Marini, R. Guerrini, A. Lehesjoki, A. Siren, M. Guipponi, A. Malafosse, P. Thoma, R. Nabbout, S. Baulac, E. Leguern, R. Guerrero, J. M. Serratosa, P. S. Reif, F. Rosenow, M. Mörzinger, M. Feucht, F. Zimprich, C. Kapser, C. J. Schankin, A. Sul, K. Smet, P. D. Jonghe, A. Jordanova, H. Caglayan, Z. Yapici, D. A. Yalcin, B. Baykan, N. Bebek, U. Ozbek, C. Gieger, H. Wichmann, T. Balschun, D. Ellinghau, A. Franke, C. Meester, T. Becker, T. F. Wienker, A. Hempelmann, H. Schulz, F. Rüschendorf, M. Leber, S. M. Pauck, H. Truck, M. R. Toliat, P. Nürnberg, G. Avanzini, B. P. C, and T. Sander
Subjects: Candidate gene, Juvenile, Genome-wide association study, Alleles, Epilepsy, ZEB2 protein, human, VRK2 protein, human, 0302 clinical medicine, genetics [Genetic Predisposition to Disease], genetics, Humans, Myoclonic Epilepsy, genetics [Epilepsy, Generalized], SCN1A protein, human, Genetics (clinical), Genetics, 0303 health sciences, genetics [Epilepsy, Absence], Myoclonic Epilepsy, Juvenile, genetics, Genetic Predisposition to Disease, General Medicine, Protein-Serine-Threonine Kinases, 3. Good health, Chemistry, Absence, genetics, Epilepsy, genetics [Myoclonic Epilepsy, Juvenile], Epilepsy, Generalized, genetics [Receptor, Muscarinic M3], genetics, NAV1.1 Voltage-Gated Sodium Channel, genetics [Homeodomain Proteins], Single-nucleotide polymorphism, genetics [NAV1.1 Voltage-Gated Sodium Channel], Protein Serine-Threonine Kinases, Biology, genetics [Protein-Serine-Threonine Kinases], 03 medical and health sciences, ddc:570, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, genetics, Repressor Protein, Allele, Molecular Biology, Alleles, Zinc Finger E-box Binding Homeobox 2, 030304 developmental biology, Homeodomain Proteins, Receptor, Muscarinic M3, genetics, Protein-Serine-Threonine Kinase, genetics, Receptor, Generalized, genetics, Genome-Wide Association Study, Homeodomain Protein, Heritability, medicine.disease, NAV1.1 Voltage-Gated Sodium Channel, Repressor Proteins, genetics [Repressor Proteins], Muscarinic M3, Epilepsy, Absence, Myoclonic epilepsy, Human medicine, Juvenile myoclonic epilepsy, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3\% and account for 20-30\% of all epilepsies. Despite their high heritability of 80\%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.
Published: 2012

7. Genetic Analysis in A Dutch Study Sample Identifies More Ulcerative Colitis Susceptibility Loci and Shows Their Additive Role in Disease Risk (vol 105, pg 395, 2010)

Author: Festen, EAM, Stokkers, PCF, van Diemen, CC, van Bodegraven, AA, Boezen, HM, Crusius, BJA, Hommes, DW, van der Woude, C.J., Balschun, T, Verspaget, HW, Schreiber, S, de Jong, DJ, Franke, A, Dijkstra, G, Wijmenga, C, Weersma, RK, and Gastroenterology & Hepatology
Published: 2010

8. Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL)

Author: Franke, A. Balschun, T. Sina, C. Ellinghaus, D. Häsler, R. Mayr, G. Albrecht, M. Wittig, M. Buchert, E. Nikolaus, S. Gieger, C. Wichmann, H.E. Sventoraityte, J. Kupcinskas, L. Onnie, C.M. Gazouli, M. Anagnou, N.P. Strachan, D. McArdle, W.L. Mathew, C.G. Rutgeerts, P. Vermeire, S. Vatn, M.H. Krawczak, M. Rosenstiel, P. Karlsen, T.H. Schreiber, S.
Abstract: We performed a genome-wide association analysis of 1,897,764 SNPs in 1,043 German ulcerative colitis (UC) cases and 1,703 controls. We discovered new associations at chromosome 7q22 (rs7809799) and at chromosome 22q13 in IL17REL (rs5771069) and confirmed these associations in six replication panels (2,539 UC cases and 5,428 controls) from different regions of Europe (overall study sample P rs7809799 = 8.81 × 10 -11 and P rs5771069 = 4.21 × 10 -8, respectively). © 2010 Nature America, Inc. All rights reserved.
Published: 2010

9. Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility

Author: Franke, A. Balschun, T. Karlsen, T.H. Sventoraityte, J. Nikolaus, S. Mayr, G. Domingues, F.S. Albrecht, M. Nothnagel, M. Ellinghaus, D. Sina, C. Onnie, C.M. Weersma, R.K. Stokkers, P.C.F. Wijmenga, C. Gazouli, M. Strachan, D. McArdle, W.L. Vermeire, S. Rutgeerts, P. Rosenstiel, P. Krawczak, M. Vatn, M.H. Mathew, C.G. Schreiber, S.
Abstract: Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 × 10 -12; OR = 1.46 (1.31-1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD. © 2008 Nature Publishing Group.
Published: 2008

10. 1400 DISCOVERY OF A DIRECT ASSOCIATION BETWEEN PRIMARY BILIARY CIRRHOSIS AND LOW BONE MASS: IDENTIFICATION OF TNFSF11/RANKL AS A RISK LOCUS FOR PATIENTS WITH PBC

Author: Hirschfield, G.M., primary, Juran, B.D., additional, Invernizzi, P., additional, Atkinson, E.J., additional, Li, Y., additional, Xie, G., additional, Kosoy, R., additional, Ransom, M., additional, Sun, Y., additional, Bianchi, I., additional, Schlicht, E.M., additional, Lleo, A., additional, Coltescu, C., additional, Bernuzzi, F., additional, Lammert, C., additional, Shigetta, R., additional, Chan, L.L., additional, Balschun, T., additional, Marconi, M., additional, Cusi, D., additional, Mason, A.L., additional, Myers, R.P., additional, Milkiewicz, P., additional, Odin, J.A., additional, Luketic, V.A., additional, Bacon, B., additional, Bodenheimer, H., additional, Liakina, V., additional, Vincent, C., additional, Levy, C., additional, Franke, A., additional, Gregerson, P.K., additional, Annese, V., additional, Gershwin, M.E., additional, de Andrade, M., additional, Amos, C.I., additional, Lazaridis, K.N., additional, Seldin, M.F., additional, and Siminovitch, K.A., additional
Published: 2012
Full Text: View/download PDF

11. No Association Between the TUCAN (CARD8) Cys10Stop Mutation and Inflammatory Bowel Disease in a Large Retrospective German and a Clinically Well-Characterized Norwegian Sample

Author: Franke, A., primary, Rosenstiel, P., additional, Balschun, T., additional, Von Kampen, O., additional, Schreiber, S., additional, Sina, C., additional, Hampe, J., additional, Karlsen, T.H., additional, Vatn, M.H., additional, and Solberg, C., additional
Published: 2007
Full Text: View/download PDF

12. Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis

Author: Beaudoin, Melissa, Goyette, Philippe, Boucher, Gabrielle, Lo, Ken Sin, Rivas, Manuel A., Stevens, Christine, Alikashani, Azadeh, Ladouceur, Martin, Ellinghaus, David, Torkvist, Leif, Goel, Gautam, Lagace, Caroline, Annese, Vito, Bitton, Alain, Begun, Jakob, Brant, Steven R., Bresso, Francesca, Cho, Judy H., Duerr, Richard H., Halfvarson, Jonas, McGovern, Dermot P. B., Radford-Smith, Graham, Schreiber, Stefan, Schumm, Philip L., Sharma, Yashoda, Silverberg, Mark S., Weersma, Rinse K., Quebec IBD Genetics Consortium, NIDDK IBD Genetics Consortium, International IBD Genetics Consortium (IIBDGC), D'Amato, Mauro, Vermeire, Severine, Franke, Andre, Lettre, Guillaume, Xavier, Ramnik J., Daly, Mark J., Rioux, John D., Aumais, G., Bernard, E. J., Bitton, A., Cohen, A., Deslandres, C., Lahaie, R., Paré, P., Rioux, J. D., Brant, S. R., Cho, J. H., Duerr, R. H., McGovern, D. P., Silverberg, M. S., Ahmad, T., Anderson, C. A., Annese, V., Baldassano, R. N., Balschun, T., Barclay, M., Barrett, J. C., Bayless, T. M., Bis, J. C., Brand, S., Bumpstead, S., Buning, C., Colombel, J. F., Cottone, M., D'Amato, M., D'Inca, R., Daly, M. J., Denson, T., Dubinsky, M., Edwards, C., Ellinghaus, D., Florin, T., Franchimont, D., Franke, A., Gearry, R., Georges, M., Glas, J., Van Gossum, A., Griffiths, A. M., Guthery, S. L., Hakonarson, H., Haritunians, T., Hugot, J. P., De Jong, D. J., Jostins, L., Kugathasan, S., Kullak-Ublick, G., Latiano, A., Laukens, D., Lawrance, I., Lee, J., Lees, C. W., Lemann, M., Levine, A., Libioulle, C., Louis, E., Mansfield, J. C., Mathew, C. G., Mitrovic, M., Montgomery, G. W., Mowat, C., Newman, W., Palmieri, O., Panés, J., Parkes, M., Phillips, A., Ponsioen, C. Y., Potocnik, U., Prescott, N. J., Proctor, D. D., Radford-Smith, G. L., Regueiro, M., Roberts, R., Rotter, J. I., Rutgeerts, P., Sanderson, J., Sans, M., Satsangi, J., Schreiber, S., Schumm, P., Seibold, F., Sharma, Y., Simms, L. A., Steinhart, A., Targan, S. R., Taylor, K. D., Torkvist, L., Vermeire, S., Halfvarson, J., Verspaget, H. W., De Vos, M., Walters, T., Wang, K., Weersma, R. K., Whiteman, D., and Wijmenga, C.
Subjects: 3. Good health
Abstract: PLoS genetics 9(9), e1003723 (2013). doi:10.1371/journal.pgen.1003723, Published by Public Library of Science, San Francisco, Calif.

13. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Author: Cordell, Heather J., Younghun, Han, Mells, George F., Yafang, Li, Hirschfield, Gideon M., Greene, Casey S., Gang, Xie, Juran 7, Brian D., Dakai Zhu, 2, Qian 2, David C., Floyd, James A. B., Morley, Katherine I., Daniele Prati 11, Ana Lleo 12, Daniele, Cusi, Eric Gershwin 15, M., Anderson 8, Carl A., Lazaridis 7, Konstantinos N., Pietro, Invernizzi, Seldin 15, Michael F., Sandford, Richard N., Amos 2, Christopher I., Siminovitch, Katherine A., Schlicht 7, Erik M., Craig Lammert, 7, Atkinson 19, Elizabeth J., Chan 19, Landon L., Mariza de Andrade 19, Tobias Balschun 20, Mason 21, Andrew L., Myers 22, Robert P., Jinyi Zhang 23, Piotr Milkiewicz 24, Jia Qu 25, Odin 26, Joseph A., Luketic 27, Velimir A., Bacon 28, Bruce R., Bodenheimer Jr 29, Henry C., Valentina Liakina 30, Catherine Vincent 31, Cynthia Levy 32, Gregersen, Peter K., Almasio, 33 Piero L., Domenico Alvaro 35, Pietro Andreone 36, Angelo Andriulli 37, Cristina Barlassina 38, Pier Maria Battezzati 39, Antonio Benedetti 40, Francesca Bernuzzi 41, Ilaria Bianchi 41, Maria Consiglia Bragazzi 42, Maurizia Brunetto 43, Savino Bruno 41, Giovanni Casella 44, Barbara Coco 43, Agostino Colli 45, Massimo Colombo 46, Silvia Colombo 47, Carmela Cursaro 36, Lory Saveria Croce, ` 48, Andrea Crosignani 39, Maria Francesca Donato 46, Gianfranco Elia 49, Luca Fabris 50, Carlo Ferrari 49, Annarosa Floreani 51, Barbara Foglieni 11, Rosanna Fontana 37, Galli, Andrea, Roberta Lazzari 51, Fabio Macaluso 34, Federica Malinverno 46, Marra, Fabio, Marco Marzioni 40, Alberto Mattalia 54, Renzo Montanari 55, Lorenzo Morini 56, Filomena Morisco 57, Mousa Hani S., 41, Luigi Muratori 36, Paolo Muratori 36, Niro 37, Grazia A., Palmieri 58, Vincenzo O., Antonio Picciotto 59, Mauro Podda 41, Piero Portincasa 58, Vincenzo Ronca 41, Floriano Rosina 60, Sonia Rossi 41, Ilaria Sogno 41, Giancarlo Spinzi 61, Marta Spreafico 11, Mario, Strazzabosco, Sonia Tarallo 60, Tarocchi, Mirko, Claudio Tiribelli 48, Pierluigi Toniutto 64, Maria Vinci 65, Massimo, Zuin, Chin Lye Ch’ng, Mesbah Rahman 68, Tom Yapp 69, Richard Sturgess 70, Christopher Healey 71, Marek, Czajkowski, Anton, Gunasekera, Pranab Gyawali 77, Purushothaman Premchand 78, Kapil Kapur 79, Richard Marley 80, Graham Foster 80, Alan Watson 81, Aruna Dias 82, Javaid Subhani 83, Rory Harvey 84, Roger McCorry 85, David Ramanaden 86, Jaber Gasem 87, Richard Evans 88, Thiriloganathan Mathialahan 89, Christopher Shorrock 90, George Lipscomb 91, Paul Southern 92, Jeremy Tibble 93, David, Gorard, Altaf Palegwala 98, Susan, Jones, Marco Carbone 101, Mohamed Dawwas 101, Graeme Alexander 101, Sunil, Dolwani, Martin Prince 104, Matthew Foxton 105, David Elphick 106, Harriet Mitchison 107, Ian Gooding 108, Mazn Karmo 109, Sushma, Saksena, Mike, Mendall, Minesh, Patel, Roland, Ede, Andrew Austin 119, Joanna, Sayer, Lorraine Hankey 122, Christopher Hovell 122, Neil Fisher 123, Martyn, Carter, Konrad Koss 126, Andrzej, Piotrowicz, Charles, Grimley, David, Neal, Guan Lim 135, Sass, Levi, Aftab Ala 138, Andrea Broad 139, Athar Saeed 139, Gordon Wood 140, Jonathan, Brown, Mark, Wilkinson, Harriet Gordon 145, John Ramage 146, Jo Ridpath 147, Theodore, Ngatchu, Bob Grover 151, Syed Shaukat 152, Ray Shidrawi 153, George, Abouda, Faiz Ali 156, Ian Rees 157, Imroz Salam 158, Mark Narain 159, Ashley, Brown, Simon Taylor Robinson 162, Simon Williams 163, Leonie Grellier 164, Paul Banim 165, Debasish Das 166, Andrew Chilton 166, Michael Heneghan 167, Howard, Curtis, Markus Gess 170, Ian, Drake, Mark, Aldersley, Mervyn, Davies, Rebecca, Jones, Alastair McNair 175, Raj Srirajaskanthan 176, Maxton, Pitcher, Sambit Sen 179, George, Bird, Adrian Barnardo 182, Paul Kitchen 182, Kevin Yoong 183, Oza, Chirag, Nurani Sivaramakrishnan 186, George MacFaul 187, David Jones 188, Amir Shah 189, Chris Evans 190, Subrata Saha 191, Katharine, Pollock, Peter, Bramley, Ashis, Mukhopadhya, Andrew, Fraser, Peter, Mills, Christopher, Shallcross, Stewart, Campbell, Andrew, Bathgate, Alan Shepherd 213, John Dillon 214, Simon Rushbrook 215, Robert Przemioslo 216 Christopher Macdonald, Jane, Metcalf, Udi Shmueli 221, Andrew, Davis, Asifabbas, Naqvi, Tom, Lee, Ryder, Stephen D., Jane Collier 231, Howard, Klass, Mary, Ninkovic, Matthew Cramp 238, Nicholas Sharer 239, Richard Aspinall 240, Patrick Goggin 240, Deb, Ghosh, Andrew Douds 243, Barbara Hoeroldt 244, Jonathan Booth 245, Earl Williams 246, Hyder Hussaini 247, William Stableforth 247, Reuben Ayres 248, Douglas Thorburn 249, Eileen Marshall 249, Andrew Burroughs 249, Steven, Mann, Martin Lombard 252, Paul Richardson 252, Imran Patanwala 252, Julia Maltby 253, Matthew Brookes 254, Ray, Mathew, Samir Vyas 257, Saket Singhal 258, Dermot, Gleeson, Sharat, Misra, Jeff, Butterworth, Keith George 265, Tim, Harding, Andrew, Douglass, Simon Panter 270, Jeremy Shearman 271, Gary Bray 272, Graham, Butcher, Daniel Forton 275, John, Mclindon, Matthew Cowan 279, Gregory Whatley 280, Aditya, Mandal, Hemant, Gupta, Pradeep, Sanghi, Sanjiv Jain 283, Steve Pereira 284, Geeta Prasad 285, Gill Watts 285, Mark Wright 286, James Neuberger 287, Fiona Gordon 288, Esther Unitt 289, Allister, Grant, Toby, Delahooke, Andrew Higham 293, Alison Brind 294, Mark Cox 295, Subramaniam Ramakrishnan 296, Alistair, King, Carole Collins 300, Simon, Whalley, Andy Li 303, Jocelyn Fraser 304, Andrew Bell 305, Voi Shim Wong 306, Amit, Singhal, Ian, Gee, Yeng Ang 312, Rupert Ransford 313, James Gotto 314, Charles, Millson, Jane Bowles 318, Caradog, Thomas, Melanie Harrison 70, Roman Galaska 71, Jennie, Kendall, Jessica, Whiteman, Caroline, Lawlor, Catherine, Gray, Keith Elliott 79, Caroline Mulvaney Jones, Lucie, Hobson, Greta Van Duyvenvoorde 90, Alison Loftus 91, Katie Seward 92, Ruth, Penn, Jane Maiden 98, Rose Damant 98, Janeane Hails 101, Rebecca, Cloudsdale, Valeria Silvestre 105, Sue Glenn 106, Eleanor Dungca 107, Natalie Wheatley 108, Helen Doyle 109, Melanie, Kent, Caroline, Hamilton, Delyth, Braim, Helen Wooldridge 117, Rachel Abrahams 117, Alison Paton 119, Nicola, Lancaster, Andrew Gibbins 122, Karen Hogben 122, Phillipa, Desousa, Florin, Muscariu, Janine, Musselwhite, Alexandra McKay 132, LaiTing Tan 135, Carole Foale 138, Jacqueline Brighton 138, Kerry Flahive 140, Estelle, Nambela, Paula, Townshend, Chris, Ford, Sophie, Holder, Caroline, Palmer, James Featherstone 147, Mariam Nasseri 151, Joy Sadeghian 153, Bronwen, Williams, Carol Thomas 156, Sally Ann Rolls 156, Abigail Hynes 159, Claire Duggan 159, Sarah Jones 159, Mary, Crossey, Glynis Stansfield 163, Carolyn MacNicol 163, Joy Wilkins 164, Elva Wilhelmsen 165, Parizade Raymode 166, Hye Jeong Lee 167, Emma, Durant, Rebecca, Bishop, Noma, Ncube, Sherill, Tripoli, Rebecca, Casey, Caroline Cowley 182, Richard Miller 183, Kathryn Houghton 188, Samantha Ducker 188, Fiona Wright 189, Bridget Bird 191, Gwen Baxter 191, Janie Keggans 191, Maggie, Hughes, Emma Grieve 196, Karin Young 196, Williams 197, D., Kate Ocker 199, Frances, Hines, Kirsty, Martin, Caron, Innes, Talal Valliani 216, Helen, Fairlamb, Sarah, Thornthwaite, Anne, Eastick, Elizabeth Tanqueray 221, Jennifer Morrison 222, Becky Holbrook 222, Julie, Browning, Kirsten, Walker, Susan, Congreave, Juliette, Verheyden, Susan, Slininger, Lizzie Stafford 231, Denise O’Donnell 231, Mark Ainsworth 231, Susan Lord 118, Linda, Kent, Linda March 238, Christine Dickson 239, Diane Simpson 239, Beverley Longhurst 240, Maria Hayes 240, Ervin, Shpuza, Nikki, White, Sarah, Besley, Sallyanne Pearson 244, Alice Wright 245, Linda Jones 245, Emma Gunter 246, Hannah Dewhurst 246, Anna Fouracres 247, Liz Farrington 247, Lyn Graves 247, Suzie Marriott 248, Marina Leoni 249, David Tyrer 252, Kate Martin 252, Lola Dali kemmery 253, Victoria Lambourne 253, Marie Green 254, Dawn, Sirdefield, Kelly Amor 255, Julie Colley 258, Bal Shinder 258, Jayne Jones 260, Marisa Mills 260, Mandy, Carnahan, Natalie Taylor 265, Kerenza Boulton 265, Julie, Tregonning, Carly Brown 270, Gayle Clifford 270, Emily Archer 271, Maria, Hamilton, Janette Curtis 278, Tracey Shewan 279, Sue Walsh 280, Karen, Warner, Kimberley Netherton 283, Mcdonald Mupudzi 286, Bridget Gunson 287, Jane Gitahi 288, Denise Gocher 289, Sally, Batham, Hilary, Pateman, Senayon, Desmennu, Jill Conder 293, Darren Clement 294, Susan Gallagher 294, Jacky Orpe 256, PuiChing Chan 296, Lynn, Currie, Lynn, O’Donohoe, Metod Oblak 300, Lisa Morgan 302, Marie Quinn 303, Isobel Amey 304, Yolanda Baird 304, Donna Cotterill 305, Lourdes Cumlat 306, Louise Winter 312, Sandra Greer 312, Katie, Spurdle, Joanna, Allison, Simon, Dyer, Helen, Sweeting, Jean, Kordula, Cordell, H. J., Han, Y., Mells, G. F., Li, Y., Hirschfield, G. M., Greene, C. S., Xie, G., Juran, B. D., Zhu, D., Qian, D. C., Floyd, J. A. B., Morley, K. I., Prati, D., Lleo, A., Cusi, D., Gershwin, M. E., Anderson, C. A., Lazaridis, K. N., Invernizzi, P., Seldin, M. F., Sandford, R. N., Amos, C. I., Siminovitch, K. A., Schlicht, E. M., Lammert, C., Atkinson, E. J., Chan, L. L., De Andrade, M., Balschun, T., Mason, A. L., Myers, R. P., Zhang, J., Milkiewicz, P., Qu, J., Odin, J. A., Luketic, V. A., Bacon, B. R., Bodenheimer, H. C., Liakina, V., Vincent, C., Levy, C., Gregersen, P. K., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Barlassina, C., Battezzati, P. M., Benedetti, A., Bernuzzi, F., Bianchi, I., Bragazzi, M. C., Brunetto, M., Bruno, S., Casella, G., Coco, B., Colli, A., Colombo, M., Colombo, S., Cursaro, C., Croce, L. S., Crosignani, A., Donato, M. 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B., Morley, Katherine I., Prati, Daniele, Lleo, Ana, Cusi, Daniele, Gershwin, M. 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B., Floyd, Katherine I., Morley, Daniele, Prati, Ana, Lleo, Daniele, Cusi, Canadian US PBC, Consortium, Italian PBC Genetics Study, Group, UK PBC, Consortium, M., Eric Gershwin, Carl A., Anderson, Konstantinos N., Lazaridi, Pietro, Invernizzi, Michael F., Seldin, Richard N., Sandford, Christopher I., Amo, Katherine A., Siminovitch, Cordell H.J., Han Y., Mells G.F., Li Y., Hirschfield G.M., Greene C.S., Xie G., Juran B.D., Zhu D., Qian D.C., Floyd J.A.B., Morley K.I., Prati D., Lleo A., Cusi D., Gershwin M.E., Anderson C.A., Lazaridis K.N., Invernizzi P., Seldin M.F., Sandford R.N., Amos C.I., Siminovitch K.A., Schlicht E.M., Lammert C., Atkinson E.J., Chan L.L., De Andrade M., Balschun T., Mason A.L., Myers R.P., Zhang J., Milkiewicz P., Qu J., Odin J.A., Luketic V.A., Bacon B.R., Bodenheimer H.C., Liakina V., Vincent C., Levy C., Gregersen P.K., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Barlassina C., Battezzati P.M., Benedetti A., Bernuzzi F., Bianchi I., Bragazzi M.C., Brunetto M., Bruno S., Casella G., Coco B., Colli A., Colombo M., Colombo S., Cursaro C., Croce L.S., Crosignani A., Donato M.F., Elia G., Fabris L., Ferrari C., Floreani A., Foglieni B., Fontana R., Galli A., Lazzari R., Macaluso F., Malinverno F., Marra F., Marzioni M., Mattalia A., Montanari R., Morini L., Morisco F., Mousa Hani S., Muratori L., Muratori P., Niro G.A., Palmieri V.O., Picciotto A., Podda M., Portincasa P., Ronca V., Rosina F., Rossi S., Sogno I., Spinzi G., Spreafico M., Strazzabosco M., Tarallo S., Tarocchi M., Tiribelli C., Toniutto P., Vinci M., Zuin M., Ch'Ng C.L., Rahman M., Yapp T., Sturgess R., Healey C., Czajkowski M., Gunasekera A., Gyawali P., Premchand P., Kapur K., Marley R., Foster G., Watson A., Dias A., Subhani J., Harvey R., McCorry R., Ramanaden D., Gasem J., Evans R., Mathialahan T., Shorrock C., Lipscomb G., Southern P., Tibble J., Gorard D., Palegwala A., Jones S., Carbone M., Dawwas M., Alexander G., Dolwani S., Prince M., Foxton M., Elphick D., Mitchison H., Gooding I., Karmo M., Saksena S., Mendall M., Patel M., Ede R., Austin A., Sayer J., Hankey L., Hovell C., Fisher N., Carter M., Koss K., Piotrowicz A., Grimley C., Neal D., Lim G., Levi S., Ala A., Broad A., Saeed A., Wood G., Brown J., Wilkinson M., Gordon H., Ramage J., Ridpath J., Ngatchu T., Grover B., Shaukat S., Shidrawi R., Abouda G., Ali F., Rees I., Salam I., Narain M., Brown A., Taylor-Robinson S., Williams S., Grellier L., Banim P., Das D., Chilton A., Heneghan M., Curtis H., Gess M., Drake I., Aldersley M., Davies M., Jones R., McNair A., Srirajaskanthan R., Pitcher M., Sen S., Bird G., Barnardo A., Kitchen P., Yoong K., Chirag O., Sivaramakrishnan N., MacFaul G., Jones D., Shah A., Evans C., Saha S., Pollock K., Bramley P., Mukhopadhya A., Fraser A., Mills P., Shallcross C., Campbell S., Bathgate A., Shepherd A., Dillon J., Rushbrook S., Przemioslo R., Macdonald C., Metcalf J., Shmueli U., Davis A., Naqvi A., Lee T., Stephen D., Collier J., Klass H., Ninkovic M., Cramp M., Sharer N., Aspinall R., Goggin P., Ghosh D., Douds A., Hoeroldt B., Booth J., Williams E., Hussaini H., Stableforth W., Ayres R., Thorburn D., Marshall E., Burroughs A., Mann S., Lombard M., Richardson P., Patanwala I., Maltby J., Brookes M., Mathew R., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Panter S., Shearman J., Bray G., Butcher G., Forton D., McLindon J., Cowan M., Whatley G., Mandal A., Gupta H., Sanghi P., Jain S., Pereira S., Prasad G., Watts G., Wright M., Neuberger J., Gordon F., Unitt E., Grant A., Delahooke T., Higham A., Brind A., Cox M., Ramakrishnan S., King A., Collins C., Whalley S., Li A., Fraser J., Bell A., Wong V.S., Singhal A., Gee I., Ang Y., Ransford R., Gotto J., Millson C., Bowles J., Thomas C., Harrison M., Galaska R., Kendall J., Whiteman J., Lawlor C., Gray C., Elliott K., Mulvaney-Jones C., Hobson L., Van Duyvenvoorde G., Loftus A., Seward K., Penn R., Maiden J., Damant R., Hails J., Cloudsdale R., Silvestre V., Glenn S., Dungca E., Wheatley N., Doyle H., Kent M., Hamilton C., Braim D., Wooldridge H., Abrahams R., Paton A., Lancaster N., Gibbins A., Hogben K., Desousa P., Muscariu F., Musselwhite J., McKay A., Tan L., Foale C., Brighton J., Flahive K., Nambela E., Townshend P., Ford C., Holder S., Palmer C., Featherstone J., Nasseri M., Sadeghian J., Williams B., Rolls S.-A., Hynes A., Duggan C., Crossey M., Stansfield G., MacNicol C., Wilkins J., Wilhelmsen E., Raymode P., Lee H.-J., Durant E., Bishop R., Ncube N., Tripoli S., Casey R., Cowley C., Miller R., Houghton K., Ducker S., Wright F., Bird B., Baxter G., Keggans J., Hughes M., Grieve E., Young K., Williams D., Ocker K., Hines F., Martin K., Innes C., Valliani T., Fairlamb H., Thornthwaite S., Eastick A., Tanqueray E., Morrison J., Holbrook B., Browning J., Walker K., Congreave S., Verheyden J., Slininger S., Stafford L., O'Donnell D., Ainsworth M., Lord S., Kent L., March L., Dickson C., Simpson D., Longhurst B., Hayes M., Shpuza E., White N., Besley S., Pearson S., Wright A., Jones L., Gunter E., Dewhurst H., Fouracres A., Farrington L., Graves L., Marriott S., Leoni M., Tyrer D., Dali-Kemmery L., Lambourne V., Green M., Sirdefield D., Amor K., Colley J., Shinder B., Jones J., Mills M., Carnahan M., Taylor N., Boulton K., Tregonning J., Brown C., Clifford G., Archer E., Hamilton M., Curtis J., Shewan T., Walsh S., Warner K., Netherton K., Mupudzi M., Gunson B., Gitahi J., Gocher D., Batham S., Pateman H., Desmennu S., Conder J., Clement D., Gallagher S., Orpe J., Chan P., Currie L., O'Donohoe L., Oblak M., Morgan L., Quinn M., Amey I., Baird Y., Cotterill D., Cumlat L., Winter L., Greer S., Spurdle K., Allison J., Dyer S., Sweeting H., Kordula J., Cordell, H, Han, Y, Mells, G, Li, Y, Hirschfield, G, Greene, C, Xie, G, Juran, B, Zhu, D, Qian, D, Floyd, J, Morley, K, Prati, D, Lleo, A, Cusi, D, Gershwin, M, Anderson, C, Lazaridis, K, Invernizzi, P, Seldin, M, Sandford, R, Amos, C, Siminovitch, K, Schlicht, E, Lammert, C, Atkinson, E, Chan, L, De Andrade, M, Balschun, T, Mason, A, Myers, R, Zhang, J, Milkiewicz, P, Qu, J, Odin, J, Luketic, V, Bacon, B, Bodenheimer, H, Liakina, V, Vincent, C, Levy, C, Gregersen, P, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, P, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, L, Crosignani, A, Donato, M, Elia, G, Fabris, L, Ferrari, C, Floreani, A, Foglieni, B, Fontana, R, Galli, A, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Mousa Hani, S, Muratori, L, Muratori, P, Niro, G, Palmieri, V, Picciotto, A, Podda, M, Portincasa, P, Ronca, V, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Spreafico, M, Strazzabosco, M, Tarallo, S, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Carbone, M, Dawwas, M, Alexander, G, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Taylor Robinson, S, Williams, S, Grellier, L, Banim, P, Das, D, Chilton, A, Heneghan, M, Curtis, H, Gess, M, Drake, I, Aldersley, M, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Jones, D, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Bathgate, A, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Stephen, D, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Thorburn, D, Marshall, E, Burroughs, A, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Neuberger, J, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Williams, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, O'Donnell, D, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali Kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, O'Donohoe, L, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, and Kordula, J
Subjects: Liver Cirrhosis, Genetics and Molecular Biology (all), pathogenesi, risk assessment EMTREE medical terms: Article, genetic association, genotype, EMTREE drug terms: chemokine receptor CCR6, genetic risk, Biochemistry, meta-analysi, primary biliary cirrhosi, chemokine receptor CCR6 [EMTREE drug terms], single nucleotide polymorphism, genetic variability, Article [risk assessment EMTREE medical terms], Liver Cirrhosis, Biliary, pathogenesis, Biliary, Chemistry (all), STAT protein GEOBASE Subject Index: disease treatment, cohort analysis, genome wide meta analysis PBC, signal transduction, gene locus, cohort analysi, CBP, Article, Physics and Astronomy (all), macrophage inflammatory protein 3alpha, Humans, controlled study, human, interleukin 27, genome, Biochemistry, Genetics and Molecular Biology (all), meta analysi, interleukin 12p40, interleukin 12, Janus kinase, meta-analysis, pathogen, genetic predisposition, major clinical study, meta analysis, primary biliary cirrhosis, disease treatment [STAT protein GEOBASE Subject Index], Genome-Wide Association Study, gene locu
Abstract: Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined, Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.
Published: 2015

14. The age related markers lipofuscin and apoptosis show different genetic architecture by QTL mapping in short-lived Nothobranchius fish

Author: Michael Wittig, Tobias Balschun, Enoch Ng'oma, Alexander Dorn, Allesandro Cellerino, Kathrin Reichwald, Andre Franke, Matthias Platzer, Ng'Oma, E, Reichwald, K, Dorn, A, Wittig, M, Balschun, T, Franke, A, Platzer, M, and Cellerino, Alessandro
Subjects: Genetics, Aging, Heterosis, Longevity, Quantitative Trait Loci, apoptosis, Overdominance, Cell Biology, Biology, Quantitative trait locus, biology.organism_classification, Phenotype, Genetic architecture, Lipofuscin, Cyprinodontiformes, Nothobranchius, In Situ Nick-End Labeling, Animals, Biomarkers, lifespan, Research Paper
Abstract: Annual fish of the genus Nothobranchius show large variations in lifespan and expression of age-related phenotypes between closely related populations. We studied N. kadleci and its sister species N. furzeri GRZ strain, and found that N.kadleci is longer-lived than the N. furzeri. Lipofuscin and apoptosis measured in the liver increased with age in N. kadleci with different profiles: lipofuscin increased linearly, while apoptosis declined in the oldest animals. More lipofuscin (P < 0.001) and apoptosis (P < 0.001) was observed in N. furzeri than in N. kadleci at 16w age. Lipofuscin and apoptotic cells were then quantified in hybrids from the mating of N. furzeri to N. kadleci. F1 individuals showed heterosis for lipofuscin but additive effects for apoptosis. These two age-related phenotypes were not correlated in F2 hybrids. Quantitative trait loci analysis of 287 F2 fish using 237 markers identified two QTL accounting for 10% of lipofuscin variance (P < 0.001) with overdominance effect. Apoptotic cells revealed three significant- and two suggestive QTL explaining 19% of variance (P < 0.001), showing additive and dominance effects, and two interacting loci. Our results show that lipofuscin and apoptosis are markers of different age-dependent biological processes controlled by different genetic mechanisms.
Published: 2014

15. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Author: Jean-Pierre Hugot, Mauro D'Amato, Carsten Büning, Cisca Wijmenga, Michel Georges, Timothy H. Florin, Christopher G. Mathew, Richard B. Gearry, Joshua C. Bis, Severine Vermeire, Deborah D. Proctor, Mark S. Silverberg, Richard H. Duerr, Laura Stronati, Hein W. Verspaget, Graham L. Radford-Smith, William G. Newman, James Lee, Talin Haritunians, Renata D'Incà, Mario Cottone, Miguel Regueiro, Frank Seibold, Jerome I. Rotter, Arie Levine, Subra Kugathasan, Philip Schumm, Soumya Raychaudhuri, Marla Dubinsky, Jack Satsangi, Cathryn Edwards, Denis Franchimont, Jürgen Glas, André Van Gossum, Edouard Louis, Todd Green, Julián Panés, David C. Whiteman, Paul Rutgeerts, Murray L. Barclay, Richard K Russell, Miquel Sans, Gerd A. Kullak-Ublick, Jean Frederick Colombel, Carl A. Anderson, Anne M. Phillips, Natalie J. Prescott, A. Hillary Steinhart, Suzanne Bumpstead, Amir Karban, Vito Annese, Thomas D. Walters, Hakon Hakonarson, Anna Latiano, David Ellinghaus, Pieter C. F. Stokkers, Leif Törkvist, Craig Mowat, Ian C. Lawrance, Kent D. Taylor, Cécile Libioulle, Rinse K. Weersma, John D. Rioux, Grant W. Montgomery, Charlie W. Lees, Marc Lémann, Ted Denson, David C. Wilson, Stephan Brand, Judy H. Cho, Steven R. Brant, Robert N. Baldassano, Theodore M. Bayless, Jeremy D. Sanderson, Tariq Ahmad, Lisa A. Simms, Stephen L. Guthery, Mark J. Daly, Rebecca L. Roberts, Debby Laukens, Jonas Halfvarson, Luke Jostins, Miles Parkes, John C. Mansfield, Albert Cohen, Eleonora M. Festen, Yashoda Sharma, Anne M. Griffiths, Andre Franke, Stephan R. Targan, Stefan Schreiber, Dermot P.B. McGovern, Jeffrey C. Barrett, Kai Wang, Martine De Vos, Tobias Balschun, Franke, A, McGovern, DP, Barrett, JC, Wang, K, Radford-Smith, GL, Ahmad, T, Lees, CW, Balschun, T, Lee, J, Roberts, R, Anderson, CA, Bis, JC, Bumpstead, S, Ellinghaus, D, Festen, EM, Georges, M, Green, T, Haritunians, T, Jostins, L, Latiano, A, Mathew, CG, Montgomery, GW, Prescott, NJ, Raychaudhuri, S, Rotter, JI, Schumm, P, Sharma, Y, Simms, LA, Taylor, KD, Whiteman, D, Wijmenga, C, Baldassano, RN, Barclay, M, Bayless, TM, Brand, S, Büning, C, Cohen, A, Colombel, JF, Cottone, M, Stronati, L, Denson, T, De Vos, M, D'Inca, R, Dubinsky, M, Edwards, C, Florin, T, Franchimont, D, Gearry, R, Glas, J, Van Gossum, A, Guthery, SL, Halfvarson, J, Verspaget, HW, Hugot, JP, Karban, A, Laukens, D, Lawrance, I, Lemann, M, Levine, A, Libioulle, C, Louis, E, Mowat, C, Newman, W, Panés, J, Phillips, A, Proctor, DD, Regueiro, M, Russell, R, Rutgeerts, P, Sanderson, J, Sans, M, Seibold, F, Steinhart, AH, Stokkers, PC, Torkvist, L, Kullak-Ublick, G, Wilson, D, Walters, T, Targan, SR, Brant, SR, Rioux, JD, D'Amato, M, Weersma, RK, Kugathasan, S, Griffiths, AM, Mansfield, JC, Vermeire, S, Duerr, RH, Silverberg, MS, Satsangi, J, Schreiber, S, Cho, JH, Annese, V, Hakonarson, H, Daly, MJ, Parkes, M, Gastroenterology and Hepatology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and University of Zurich
Subjects: Candidate gene, Genetic Linkage, PROTEIN, Genome-wide association study, Inflammatory bowel disease, Genome, ACTIVATION, 0302 clinical medicine, Crohn Disease, SEQUENCE VARIANTS, Genetics, 0303 health sciences, NEDD4 FAMILY, COMMON VARIANTS, ASSOCIATION, 3. Good health, 030220 oncology & carcinogenesis, 10076 Center for Integrative Human Physiology, Computational Biology, Genetic Loci, Genetic Variation, Genome, Human, Humans, Reproducibility of Results, Genetic Predisposition to Disease, Genome-Wide Association Study, inflammatory-bowel-disease sequence variants common variants nedd4 family association gene identification receptor protein activation, Human, Locus (genetics), 610 Medicine & health, Biology, 03 medical and health sciences, 1311 Genetics, Genetic linkage, medicine, 030304 developmental biology, Genetic association, IDENTIFICATION, RECEPTOR, medicine.disease, GENE, Settore MED/03 - Genetica Medica, 10199 Clinic for Clinical Pharmacology and Toxicology, 570 Life sciences, biology, Human genome, genome-wide scan.meta-analysis.crohn's disease, INFLAMMATORY-BOWEL-DISEASE
Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
Published: 2010

16. The age related markers lipofuscin and apoptosis show different genetic architecture by QTL mapping in short-lived Nothobranchius fish.

Author: Ng'oma E, Reichwald K, Dorn A, Wittig M, Balschun T, Franke A, Platzer M, and Cellerino A
Subjects: Animals, Biomarkers analysis, In Situ Nick-End Labeling, Lipofuscin metabolism, Longevity genetics, Quantitative Trait Loci, Aging genetics, Apoptosis genetics, Cyprinodontiformes genetics, Lipofuscin analysis
Abstract: Annual fish of the genus Nothobranchius show large variations in lifespan and expression of age-related phenotypes between closely related populations. We studied N. kadleci and its sister species N. furzeri GRZ strain, and found that N.kadleci is longer-lived than the N. furzeri. Lipofuscin and apoptosis measured in the liver increased with age in N. kadleci with different profiles: lipofuscin increased linearly, while apoptosis declined in the oldest animals. More lipofuscin (P<0.001) and apoptosis (P<0.001) was observed in N. furzeri than in N. kadleci at 16w age. Lipofuscin and apoptotic cells were then quantified in hybrids from the mating of N. furzeri to N. kadleci. F₁individuals showed heterosis for lipofuscin but additive effects for apoptosis. These two age-related phenotypes were not correlated in F₂ hybrids. Quantitative trait loci analysis of 287 F₂ fish using 237 markers identified two QTL accounting for 10% of lipofuscin variance (P<0.001) with overdominance effect. Apoptotic cells revealed three significant- and two suggestive QTL explaining 19% of variance (P<0.001), showing additive and dominance effects, and two interacting loci. Our results show that lipofuscin and apoptosis are markers of different age-dependent biological processes controlled by different genetic mechanisms.
Published: 2014
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17. Replication study of ulcerative colitis risk loci in a Lithuanian-Latvian case-control sample.

Author: Skieceviciene J, Kiudelis G, Ellinghaus E, Balschun T, Jonaitis LV, Zvirbliene A, Denapiene G, Leja M, Pranculiene G, Kalibatas V, Saadati H, Ellinghaus D, Andersen V, Valantinas J, Irnius A, Derovs A, Tamelis A, Schreiber S, Kupcinskas L, and Franke A
Subjects: Adult, Case-Control Studies, Europe, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Prognosis, Risk Factors, Biomarkers metabolism, Colitis, Ulcerative genetics, Polymorphism, Single Nucleotide genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 22 genetics
Abstract: Background: Differences between populations might be reflected in their different genetic risk maps to complex diseases, for example, inflammatory bowel disease. We here investigated the role of known inflammatory bowel disease-associated single nucleotide polymorphisms (SNPs) in a subset of patients with ulcerative colitis (UC) from the Northeastern European countries Lithuania and Latvia and evaluated possible epistatic interactions between these genetic variants., Methods: We investigated 77 SNPs derived from 5 previously published genome-wide association studies for Crohn's disease and UC. Our study panel comprised 444 Lithuanian and Latvian patients with UC and 1154 healthy controls. Single marker case-control association and SNP-SNP epistasis analyses were performed., Results: We found 14 SNPs tagging 9 loci, including 21q21.1, NKX2-3, MST1, the HLA region, 1p36.13, IL10, JAK2, ORMDL3, and IL23R, to be associated with UC. Interestingly, the association of UC with previously identified variants in the HLA region was not the strongest association in our study (P = 4.34 × 10, odds ratio [OR] = 1.25), which is in contrast to all previously published studies. No association with any disease subphenotype was found. SNP-SNP interaction analysis showed significant epistasis between SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes and increased risk for UC (P = 1.64 × 10, OR = 2.44). The association has been confirmed in the Danish study group (P = 0.04, OR = 3.25)., Conclusions: We confirmed the association of the 9 loci (21q21.1, 1p36.13, NKX2-3, MST1, the HLA region, IL10, JAK2, ORMDL3, and IL23R) with UC in the Lithuanian-Latvian population. SNP-SNP interaction analyses showed that the combination of SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes increase the risk for UC.
Published: 2013
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18. Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.

Author: Ellinghaus D, Folseraas T, Holm K, Ellinghaus E, Melum E, Balschun T, Laerdahl JK, Shiryaev A, Gotthardt DN, Weismüller TJ, Schramm C, Wittig M, Bergquist A, Björnsson E, Marschall HU, Vatn M, Teufel A, Rust C, Gieger C, Wichmann HE, Runz H, Sterneck M, Rupp C, Braun F, Weersma RK, Wijmenga C, Ponsioen CY, Mathew CG, Rutgeerts P, Vermeire S, Schrumpf E, Hov JR, Manns MP, Boberg KM, Schreiber S, Franke A, and Karlsen TH
Subjects: Belgium, Case-Control Studies, Cholangitis, Sclerosing epidemiology, Cholangitis, Sclerosing ethnology, Colitis, Ulcerative epidemiology, Colitis, Ulcerative ethnology, Comorbidity, Genetic Loci genetics, Genetic Predisposition to Disease ethnology, Genotype, Germany, Humans, Netherlands, Norway, Polymorphism, Single Nucleotide genetics, Risk Factors, Transcription Factor 4, United Kingdom, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Cholangitis, Sclerosing genetics, Colitis, Ulcerative genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Receptors, G-Protein-Coupled genetics, Transcription Factors genetics
Abstract: Unlabelled: Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 (GPR35); P = 3.0 × 10(-9) in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 (TCF4); P = 2.61 × 10(-8) , OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor., Conclusion: By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis., (Copyright © 2012 American Association for the Study of Liver Diseases.)
Published: 2013
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19. Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus.

Author: von Kampen O, Buch S, Nothnagel M, Azocar L, Molina H, Brosch M, Erhart W, von Schönfels W, Egberts J, Seeger M, Arlt A, Balschun T, Franke A, Lerch MM, Mayerle J, Kratzer W, Boehm BO, Huse K, Schniewind B, Tiemann K, Jiang ZY, Han TQ, Mittal B, Srivastava A, Fenger M, Jørgensen T, Schirin-Sokhan R, Tönjes A, Wittenburg H, Stumvoll M, Kalthoff H, Lammert F, Tepel J, Puschel K, Becker T, Schreiber S, Platzer M, Völzke H, Krawczak M, Miquel JF, Schafmayer C, and Hampe J
Subjects: ATP Binding Cassette Transporter, Subfamily G, Member 5, ATP Binding Cassette Transporter, Subfamily G, Member 8, Alleles, Alternative Splicing, Case-Control Studies, Cell Line, Gallstones metabolism, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, ATP-Binding Cassette Transporters genetics, Cholesterol metabolism, Gallstones genetics, Lipoproteins genetics
Abstract: Unlabelled: The sterolin locus (ABCG5/ABCG8) confers susceptibility for cholesterol gallstone disease in humans. Both the responsible variant and the molecular mechanism causing an increased incidence of gallstones in these patients have as yet not been identified. Genetic mapping utilized patient samples from Germany (2,808 cases, 2,089 controls), Chile (680 cases, 442 controls), Denmark (366 cases, 766 controls), India (247 cases, 224 controls), and China (280 cases, 244 controls). Analysis of allelic imbalance in complementary DNA (cDNA) samples from human liver (n = 22) was performed using pyrosequencing. Transiently transfected HEK293 cells were used for [(3) H]-cholesterol export assays, analysis of protein expression, and localization of allelic constructs. Through fine mapping in German and Chilean samples, an ∼250 kB disease-associated interval could be defined for this locus. Lack of allelic imbalance or allelic splicing of the ABCG5 and ABCG8 transcripts in human liver limited the search to coding single nucleotide polymorphisms. Subsequent mutation detection and genotyping yielded two disease-associated variants: ABCG5-R50C (P = 4.94 × 10(-9) ) and ABCG8-D19H (P = 1.74 × 10(-10) ) in high pairwise linkage disequilibrium (r(2) = 0.95). [(3) H]-cholesterol export assays of allelic constructs harboring these genetic candidate variants demonstrated increased transport activity (3.2-fold, P = 0.003) only for the ABCG8-19H variant, which was also superior in nested logistic regression models in German (P = 0.018), Chilean (P = 0.030), and Chinese (P = 0.040) patient samples., Conclusion: This variant thus provides a molecular basis for biliary cholesterol hypersecretion as the mechanism for cholesterol gallstone formation, thereby drawing a link between "postgenomic" and "pregenomic" pathophysiological knowledge about this common complex disorder. (HEPATOLOGY 2012)., (Copyright © 2012 American Association for the Study of Liver Diseases.)
Published: 2013
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20. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32.

Author: Steffens M, Leu C, Ruppert AK, Zara F, Striano P, Robbiano A, Capovilla G, Tinuper P, Gambardella A, Bianchi A, La Neve A, Crichiutti G, de Kovel CG, Kasteleijn-Nolst Trenité D, de Haan GJ, Lindhout D, Gaus V, Schmitz B, Janz D, Weber YG, Becker F, Lerche H, Steinhoff BJ, Kleefuß-Lie AA, Kunz WS, Surges R, Elger CE, Muhle H, von Spiczak S, Ostertag P, Helbig I, Stephani U, Møller RS, Hjalgrim H, Dibbens LM, Bellows S, Oliver K, Mullen S, Scheffer IE, Berkovic SF, Everett KV, Gardiner MR, Marini C, Guerrini R, Lehesjoki AE, Siren A, Guipponi M, Malafosse A, Thomas P, Nabbout R, Baulac S, Leguern E, Guerrero R, Serratosa JM, Reif PS, Rosenow F, Mörzinger M, Feucht M, Zimprich F, Kapser C, Schankin CJ, Suls A, Smets K, De Jonghe P, Jordanova A, Caglayan H, Yapici Z, Yalcin DA, Baykan B, Bebek N, Ozbek U, Gieger C, Wichmann HE, Balschun T, Ellinghaus D, Franke A, Meesters C, Becker T, Wienker TF, Hempelmann A, Schulz H, Rüschendorf F, Leber M, Pauck SM, Trucks H, Toliat MR, Nürnberg P, Avanzini G, Koeleman BP, and Sander T
Subjects: Alleles, Epilepsy, Absence genetics, Genetic Predisposition to Disease genetics, Homeodomain Proteins genetics, Humans, Myoclonic Epilepsy, Juvenile genetics, NAV1.1 Voltage-Gated Sodium Channel genetics, Protein Serine-Threonine Kinases genetics, Receptor, Muscarinic M3 genetics, Repressor Proteins genetics, Zinc Finger E-box Binding Homeobox 2, Epilepsy, Generalized genetics, Genome-Wide Association Study
Abstract: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.
Published: 2012
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21. Genetic variants in Protocadherin-1, bronchial hyper-responsiveness, and asthma subphenotypes in German children.

Author: Toncheva AA, Suttner K, Michel S, Klopp N, Illig T, Balschun T, Vogelberg C, von Berg A, Bufe A, Heinzmann A, Laub O, Rietschel E, Simma B, Frischer T, Genuneit J, von Mutius E, and Kabesch M
Subjects: Child, Chromosomes, Human, Pair 5 genetics, Cytokines genetics, Disease Progression, Female, Genetic Association Studies, Germany, High-Throughput Nucleotide Sequencing, Humans, Linkage Disequilibrium, Male, Phenotype, Polymorphism, Genetic, Protocadherins, Asthma physiopathology, Bronchial Hyperreactivity genetics, Cadherins genetics
Abstract: Background: Recently, Protocadherin-1 (PCDH1) was reported as a novel susceptibility gene for bronchial hyper-responsiveness (BHR) and asthma. PCDH1 is located on chromosome 5q31-33, in the vicinity of several known candidate genes for asthma and allergy. To exclude that the associations observed for PCDH1 originate from the nearby cytokine cluster, an extensive linkage disequilibrium (LD) analysis was performed. Effects of polymorphisms in PCDH1 on asthma, BHR, and related phenotypes were studied comprehensively., Methods: Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping, and imputation. LD was assessed by Haploview 4.2 software. Associations were investigated in a population of 1454 individuals (763 asthmatics) from two German study populations [MAGICS and International Study of Asthma and Allergies in Childhood phase II (ISAAC II)] using logistic regression to model additive effects., Results: No relevant LD between PCDH1 tagging polymorphisms and 98 single nucleotide polymorphisms within the cytokine cluster was detected. While BHR was not associated with PCDH1 polymorphisms, significant associations with subphenotypes of asthma were observed., Conclusion: Protocadherin-1 polymorphisms may specifically affect the development of non-atopic asthma in children. Functional studies are needed to further investigate the role of PCDH1 in BHR and asthma development., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)
Published: 2012
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22. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

Author: Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Büning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, and Cho JH
Subjects: Colitis, Ulcerative genetics, Colitis, Ulcerative immunology, Colitis, Ulcerative microbiology, Colitis, Ulcerative physiopathology, Crohn Disease genetics, Crohn Disease immunology, Crohn Disease microbiology, Crohn Disease physiopathology, Genome, Human genetics, Haplotypes genetics, Humans, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases physiopathology, Mycobacterium pathogenicity, Mycobacterium Infections genetics, Mycobacterium Infections microbiology, Mycobacterium tuberculosis immunology, Mycobacterium tuberculosis pathogenicity, Phenotype, Polymorphism, Single Nucleotide genetics, Reproducibility of Results, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Host-Pathogen Interactions genetics, Host-Pathogen Interactions immunology, Inflammatory Bowel Diseases genetics, Inflammatory Bowel Diseases microbiology, Mycobacterium immunology
Abstract: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
Published: 2012
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23. Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci.

Author: Ellinghaus D, Ellinghaus E, Nair RP, Stuart PE, Esko T, Metspalu A, Debrus S, Raelson JV, Tejasvi T, Belouchi M, West SL, Barker JN, Kõks S, Kingo K, Balschun T, Palmieri O, Annese V, Gieger C, Wichmann HE, Kabesch M, Trembath RC, Mathew CG, Abecasis GR, Weidinger S, Nikolaus S, Schreiber S, Elder JT, Weichenthal M, Nothnagel M, and Franke A
Subjects: Exons genetics, Female, Gene Expression genetics, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, Crohn Disease genetics, Genetic Loci, Genetic Predisposition to Disease genetics, Psoriasis genetics
Abstract: Psoriasis (PS) and Crohn disease (CD) have been shown to be epidemiologically, pathologically, and therapeutically connected, but little is known about their shared genetic causes. We performed meta-analyses of five published genome-wide association studies on PS (2,529 cases and 4,955 controls) and CD (2,142 cases and 5,505 controls), followed up 20 loci that showed strongest evidence for shared disease association and, furthermore, tested cross-disease associations for previously reported PS and CD risk alleles in additional 6,115 PS cases, 4,073 CD cases, and 10,100 controls. We identified seven susceptibility loci outside the human leukocyte antigen region (9p24 near JAK2, 10q22 at ZMIZ1, 11q13 near PRDX5, 16p13 near SOCS1, 17q21 at STAT3, 19p13 near FUT2, and 22q11 at YDJC) shared between PS and CD with genome-wide significance (p < 5 × 10(-8)) and confirmed four already established PS and CD risk loci (IL23R, IL12B, REL, and TYK2). Three of the shared loci are also genome-wide significantly associated with PS alone (10q22 at ZMIZ1, p(rs1250544) = 3.53 × 10(-8), 11q13 near PRDX5, p(rs694739) = 3.71 × 10(-09), 22q11 at YDJC, p(rs181359) = 8.02 × 10(-10)). In addition, we identified one susceptibility locus for CD (16p13 near SOCS1, p(rs4780355) = 4.99 × 10(-8)). Refinement of association signals identified shared genome-wide significant associations for exonic SNPs at 10q22 (ZMIZ1) and in silico expression quantitative trait locus analyses revealed that the associations at ZMIZ1 and near SOCS1 have a potential functional effect on gene expression. Our results show the usefulness of joint analyses of clinically distinct immune-mediated diseases and enlarge the map of shared genetic risk loci., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Published: 2012
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24. A case-only study of gene-environment interaction between genetic susceptibility variants in NOD2 and cigarette smoking in Crohn's disease aetiology.

Author: Helbig KL, Nothnagel M, Hampe J, Balschun T, Nikolaus S, Schreiber S, Franke A, and Nöthlings U
Subjects: Adult, Alleles, Case-Control Studies, Crohn Disease etiology, Female, Gene Frequency, Genotype, Heterozygote, Humans, Male, Odds Ratio, Polymorphism, Genetic, Risk Factors, Crohn Disease genetics, Gene-Environment Interaction, Genetic Predisposition to Disease, Nod2 Signaling Adaptor Protein genetics, Smoking
Abstract: Background: Genetic variation in NOD2 and cigarette smoking are well-established risk factors for the development of Crohn's disease (CD). However, little is known about a potential interaction between these risk factors. We investigated gene-environment interactions between CD-associated NOD2 alleles and cigarette smoking in a large sample of patients with CD., Methods: Three previously reported CD-associated variants in NOD2 (R702W, G908R, 1007fs) were genotyped in 1636 patients with CD continuously recruited between 1995 and 2010 based on physician referral. Data on history of smoking behaviour was obtained for all participants through a written questionnaire. Using a case-only design, we performed logistic regression analyses to investigate statistical interactions between NOD2 risk alleles and smoking status., Results: We detected a significant negative interaction between carriership of at least one of the NOD2 risk alleles and history of ever having smoked (OR = 0.71; p = 0.005) as well as smoking at the time of CD diagnosis (OR = 0.68; p = 0.005). Subsequent separate analyses of the three variants revealed a significant negative interaction between the 1007fs variant and history of ever having smoked (OR = 0.64; p = 9 × 10-4) and smoking at the time of CD diagnosis (OR = 0.53; p = 7 × 10-5)., Conclusions: The observed significant negative gene-environment interaction suggests that the risk increase for CD conferred simultaneously by cigarette smoking and the 1007fs NOD2 polymorphism is smaller than expected and may point to a biological interaction. Our findings warrant further investigation in epidemiological and functional studies to elucidate pathophysiology as well as to aid in the development of recommendations for disease prevention.
Published: 2012
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25. PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohn's disease and affect NF-κB and XBP1 binding sites.

Author: Glas J, Seiderer J, Czamara D, Pasciuto G, Diegelmann J, Wetzke M, Olszak T, Wolf C, Müller-Myhsok B, Balschun T, Achkar JP, Kamboh MI, Franke A, Duerr RH, and Brand S
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Binding Sites, Child, Epistasis, Genetic, Female, Gene Expression, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Receptors, Prostaglandin E, EP4 Subtype metabolism, Regulatory Factor X Transcription Factors, Sequence Analysis, DNA, X-Box Binding Protein 1, Young Adult, Chromosomes, Human, Pair 5 genetics, Crohn Disease genetics, DNA-Binding Proteins metabolism, NF-kappa B metabolism, Polymorphism, Single Nucleotide, Receptors, Prostaglandin E, EP4 Subtype genetics, Transcription Factors metabolism
Abstract: Background: Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes., Methodology/principal Findings: A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10⁻⁵; 0.76 [0.67-0.87]) and of rs7720838 (p = 6.91×10⁻⁴; 0.81 [0.71-0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10⁻⁷ for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD., Conclusions/significance: We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if changes in PTGER4 expression modulate CD susceptibility.
Published: 2012
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26. Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry.

Author: Hunt KA, Smyth DJ, Balschun T, Ban M, Mistry V, Ahmad T, Anand V, Barrett JC, Bhaw-Rosun L, Bockett NA, Brand OJ, Brouwer E, Concannon P, Cooper JD, Dias KR, van Diemen CC, Dubois PC, Edkins S, Fölster-Holst R, Fransen K, Glass DN, Heap GA, Hofmann S, Huizinga TW, Hunt S, Langford C, Lee J, Mansfield J, Marrosu MG, Mathew CG, Mein CA, Müller-Quernheim J, Nutland S, Onengut-Gumuscu S, Ouwehand W, Pearce K, Prescott NJ, Posthumus MD, Potter S, Rosati G, Sambrook J, Satsangi J, Schreiber S, Shtir C, Simmonds MJ, Sudman M, Thompson SD, Toes R, Trynka G, Vyse TJ, Walker NM, Weidinger S, Zhernakova A, Zoledziewska M, Weersma RK, Gough SC, Sawcer S, Wijmenga C, Parkes M, Cucca F, Franke A, Deloukas P, Rich SS, Todd JA, and van Heel DA
Subjects: Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Risk Factors, White People, Acetylesterase genetics, Autoimmune Diseases genetics, Genetic Variation
Published: 2011
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27. Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study.

Author: Andersen V, Ernst A, Sventoraityte J, Kupcinskas L, Jacobsen BA, Krarup HB, Vogel U, Jonaitis L, Denapiene G, Kiudelis G, Balschun T, and Franke A
Subjects: Adult, Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Colitis, Ulcerative genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide, White People genetics
Abstract: Background: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance., Methods: Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing., Results: The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).No SNP reached genome-wide significance in the combined analyses of all the panels., Conclusions: This replication study supports an important role for the studied rs5771069 (IL17REL) SNP, but not for rs7809799 (SMURF1/KPNA7), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (TCP11) in UC etiology between the Nordic and the other European populations.
Published: 2011
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28. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Author: Melum E, Franke A, Schramm C, Weismüller TJ, Gotthardt DN, Offner FA, Juran BD, Laerdahl JK, Labi V, Björnsson E, Weersma RK, Henckaerts L, Teufel A, Rust C, Ellinghaus E, Balschun T, Boberg KM, Ellinghaus D, Bergquist A, Sauer P, Ryu E, Hov JR, Wedemeyer J, Lindkvist B, Wittig M, Porte RJ, Holm K, Gieger C, Wichmann HE, Stokkers P, Ponsioen CY, Runz H, Stiehl A, Wijmenga C, Sterneck M, Vermeire S, Beuers U, Villunger A, Schrumpf E, Lazaridis KN, Manns MP, Schreiber S, and Karlsen TH
Subjects: Apoptosis Regulatory Proteins genetics, Bcl-2-Like Protein 11, Cohort Studies, Gene Expression Profiling, Genetic Loci, HLA Antigens genetics, Hepatocyte Growth Factor genetics, Humans, Membrane Proteins genetics, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins genetics, Cholangitis, Sclerosing genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study
Abstract: Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10⁻¹⁶ and P = 4.1 × 10⁻⁸, respectively).
Published: 2011
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29. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

Author: Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, Anderson CA, Bis JC, Bumpstead S, Ellinghaus D, Festen EM, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew CG, Montgomery GW, Prescott NJ, Raychaudhuri S, Rotter JI, Schumm P, Sharma Y, Simms LA, Taylor KD, Whiteman D, Wijmenga C, Baldassano RN, Barclay M, Bayless TM, Brand S, Büning C, Cohen A, Colombel JF, Cottone M, Stronati L, Denson T, De Vos M, D'Inca R, Dubinsky M, Edwards C, Florin T, Franchimont D, Gearry R, Glas J, Van Gossum A, Guthery SL, Halfvarson J, Verspaget HW, Hugot JP, Karban A, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, Mowat C, Newman W, Panés J, Phillips A, Proctor DD, Regueiro M, Russell R, Rutgeerts P, Sanderson J, Sans M, Seibold F, Steinhart AH, Stokkers PC, Torkvist L, Kullak-Ublick G, Wilson D, Walters T, Targan SR, Brant SR, Rioux JD, D'Amato M, Weersma RK, Kugathasan S, Griffiths AM, Mansfield JC, Vermeire S, Duerr RH, Silverberg MS, Satsangi J, Schreiber S, Cho JH, Annese V, Hakonarson H, Daly MJ, and Parkes M
Subjects: Computational Biology, Crohn Disease etiology, Genetic Linkage, Genetic Variation, Humans, Reproducibility of Results, Crohn Disease genetics, Genetic Loci genetics, Genetic Predisposition to Disease, Genome, Human genetics, Genome-Wide Association Study
Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
Published: 2010
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30. Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis.

Author: Hov JR, Keitel V, Laerdahl JK, Spomer L, Ellinghaus E, ElSharawy A, Melum E, Boberg KM, Manke T, Balschun T, Schramm C, Bergquist A, Weismüller T, Gotthardt D, Rust C, Henckaerts L, Onnie CM, Weersma RK, Sterneck M, Teufel A, Runz H, Stiehl A, Ponsioen CY, Wijmenga C, Vatn MH, Stokkers PC, Vermeire S, Mathew CG, Lie BA, Beuers U, Manns MP, Schreiber S, Schrumpf E, Häussinger D, Franke A, and Karlsen TH
Subjects: Adolescent, Adult, Aged, Amino Acid Sequence, Animals, Cattle, Child, Cholangitis, Sclerosing complications, Cholangitis, Sclerosing metabolism, Chromosomes, Human, Pair 2 genetics, Colitis, Ulcerative complications, Dogs, Female, Gene Expression Regulation, Humans, Male, Mice, Middle Aged, Models, Molecular, Protein Conformation, Receptors, G-Protein-Coupled chemistry, Receptors, G-Protein-Coupled metabolism, Young Adult, Cholangitis, Sclerosing genetics, DNA Mutational Analysis, Mutation, Receptors, G-Protein-Coupled genetics
Abstract: Background: TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC, as well as functionally characterize detected variants., Methodology/principal Findings: Complete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor model, and introduced mutated TGR5 constructs into human epithelial cell lines. By using confocal microscopy, flow cytometry and a cAMP-sensitive luciferase assay, five of the nonsynonymous mutations (W83R, V178M, A217P, S272G and Q296X) were found to reduce or abolish TGR5 function. Fine-mapping of the previously reported PSC and UC associated locus at chromosome 2q35 in large patient panels revealed an overall association between the TGR5 single-nucleotide polymorphism rs11554825 and PSC (odds ratio = 1.14, 95% confidence interval: 1.03-1.26, p = 0.010) and UC (odds ratio = 1.19, 95% confidence interval 1.11-1.27, p = 8.5 x 10(-7)), but strong linkage disequilibrium precluded demarcation of TGR5 from neighboring genes., Conclusions/significance: Resequencing of TGR5 along with functional investigations of novel variants provided unique insight into an important candidate gene for several inflammatory and metabolic conditions. While significant TGR5 associations were detected in both UC and PSC, further studies are needed to conclusively define the role of TGR5 variation in these diseases.
Published: 2010
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31. Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL).

Author: Franke A, Balschun T, Sina C, Ellinghaus D, Häsler R, Mayr G, Albrecht M, Wittig M, Buchert E, Nikolaus S, Gieger C, Wichmann HE, Sventoraityte J, Kupcinskas L, Onnie CM, Gazouli M, Anagnou NP, Strachan D, McArdle WL, Mathew CG, Rutgeerts P, Vermeire S, Vatn MH, Krawczak M, Rosenstiel P, Karlsen TH, and Schreiber S
Subjects: Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Risk Factors, Chromosomes, Human, Pair 22, Chromosomes, Human, Pair 7, Colitis, Ulcerative genetics, Polymorphism, Single Nucleotide, Receptors, Interleukin-17 genetics
Abstract: We performed a genome-wide association analysis of 1,897,764 SNPs in 1,043 German ulcerative colitis (UC) cases and 1,703 controls. We discovered new associations at chromosome 7q22 (rs7809799) and at chromosome 22q13 in IL17REL (rs5771069) and confirmed these associations in six replication panels (2,539 UC cases and 5,428 controls) from different regions of Europe (overall study sample P(rs7809799) = 8.81 x 10(-11) and P(rs5771069) = 4.21 x 10(-8), respectively).
Published: 2010
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32. Genome-wide association analysis in primary sclerosing cholangitis.

Author: Karlsen TH, Franke A, Melum E, Kaser A, Hov JR, Balschun T, Lie BA, Bergquist A, Schramm C, Weismüller TJ, Gotthardt D, Rust C, Philipp EE, Fritz T, Henckaerts L, Weersma RK, Stokkers P, Ponsioen CY, Wijmenga C, Sterneck M, Nothnagel M, Hampe J, Teufel A, Runz H, Rosenstiel P, Stiehl A, Vermeire S, Beuers U, Manns MP, Schrumpf E, Boberg KM, and Schreiber S
Subjects: Bile metabolism, Biliary Tract metabolism, Case-Control Studies, Cell Line, Chi-Square Distribution, Cholangitis, Sclerosing immunology, Colitis, Ulcerative genetics, Europe, Gene Expression Profiling methods, Gene Frequency, Gene Silencing, Genetic Predisposition to Disease, Genome-Wide Association Study, Glypicans genetics, HLA Antigens genetics, Humans, Inflammation Mediators metabolism, Odds Ratio, Oligonucleotide Array Sequence Analysis, Phenotype, Risk Assessment, Risk Factors, Biliary Tract immunology, Cholangitis, Sclerosing genetics, Polymorphism, Single Nucleotide
Abstract: Background & Aims: We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of a genome-wide association analysis of single nucleotide polymorphism (SNP) markers., Methods: A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 (Affymetrix, Santa Clara, CA) were genotyped in 285 Norwegian PSC patients and 298 healthy controls. Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia (137 PSC cases and 368 controls), Belgium/The Netherlands (229 PSC cases and 735 controls), and Germany (400 cases and 1832 controls)., Results: The strongest associations were detected near HLA-B at chromosome 6p21 (rs3099844: odds ratio [OR], 4.8; 95% confidence interval [CI], 3.6-6.5; P = 2.6 x 10(-26); and rs2844559: OR, 4.7; 95% CI, 3.5-6.4; P = 4.2 x 10(-26) in the discovery panel). Outside the HLA complex, rs9524260 at chromosome 13q31 showed significant associations in 3 of 4 study panels. Lentiviral silencing of glypican 6, encoded at this locus, led to the up-regulation of proinflammatory markers in a cholangiocyte cell line. Of 15 established ulcerative colitis susceptibility loci, significant replication was obtained at chromosomes 2q35 and 3p21 (rs12612347: OR, 1.26; 95% CI, 1.06-1.50; and rs3197999: OR, 1.22; 95% CI, 1.02-1.47, respectively), with circumstantial evidence supporting the G-protein-coupled bile acid receptor 1 and macrophage-stimulating 1, respectively, as the likely disease genes., Conclusions: Strong HLA associations and a subset of genes involved in bile homeostasis and other inflammatory conditions constitute key components of the genetic architecture of PSC., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Published: 2010
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33. Genetic analysis in a Dutch study sample identifies more ulcerative colitis susceptibility loci and shows their additive role in disease risk.

Author: Festen EA, Stokkers PC, van Diemen CC, van Bodegraven AA, Boezen HM, Crusius BJ, Hommes DW, van der Woude CJ, Balschun T, Verspaget HW, Schreiber S, de Jong DJ, Franke A, Dijkstra G, Wijmenga C, and Weersma RK
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Child, Preschool, Cohort Studies, Colitis, Ulcerative therapy, Female, Gene Dosage genetics, Humans, Male, Middle Aged, Netherlands, Phenotype, Young Adult, Colitis, Ulcerative genetics, Colitis, Ulcerative pathology, Genetic Loci genetics, Genetic Predisposition to Disease genetics, Polymorphism, Single Nucleotide genetics
Abstract: Objectives: Genetic susceptibility is known to make a major contribution to the pathogenesis of ulcerative colitis (UC). Recently, three studies, including a genome-wide association study (GWAS), reported novel UC risk loci., Methods: The top-20 single-nucleotide polymorphisms (SNPs) from the first UC-GWAS were genotyped, as part of the study's replication phase, in 561 UC cases and 728 controls from our Dutch UC study sample. We genotyped eight SNPs identified in two more studies, in these individuals, and replicated all significantly associated SNPs in an additional 894 UC cases and 1,174 controls from our Dutch UC study sample. A combined analysis for all patients (n=1,455) and controls (n=1,902) was performed. Dose-response models were constructed with the associated risk alleles., Results: We found 12 SNPs tagging ten loci, including HLA-DRA, IL10, IL23R, JAK2, S100Z, ARPC2, and ECM1, to be associated with UC. We identified 10q26, flagged by the UC-GWAS but not confirmed in its replication phase, as a UC locus and found a trend toward association for GAS7. No association with disease localization or severity was found. The dose-response models show that individuals carrying 11 or more risk alleles have an odds ratio of 8.2 (confidence interval 3.0-22.8) for UC susceptibility., Conclusions: We confirmed the association of multiple loci with UC in the Dutch population and found evidence for association of 10q26 and a trend suggesting association for GAS7. Genetic models show that multiple risk loci in an individual increase the risk for developing UC.
Published: 2010
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34. Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility.

Author: Franke A, Balschun T, Karlsen TH, Sventoraityte J, Nikolaus S, Mayr G, Domingues FS, Albrecht M, Nothnagel M, Ellinghaus D, Sina C, Onnie CM, Weersma RK, Stokkers PC, Wijmenga C, Gazouli M, Strachan D, McArdle WL, Vermeire S, Rutgeerts P, Rosenstiel P, Krawczak M, Vatn MH, Mathew CG, and Schreiber S
Subjects: Base Sequence, Case-Control Studies, Humans, Actin-Related Protein 2-3 Complex genetics, Colitis, Ulcerative genetics, Genetic Predisposition to Disease, Interleukin-10 genetics, Mutation genetics
Abstract: Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 x 10(-12); OR = 1.46 (1.31-1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD.
Published: 2008
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35. Genome-wide association analysis in sarcoidosis and Crohn's disease unravels a common susceptibility locus on 10p12.2.

Author: Franke A, Fischer A, Nothnagel M, Becker C, Grabe N, Till A, Lu T, Müller-Quernheim J, Wittig M, Hermann A, Balschun T, Hofmann S, Niemiec R, Schulz S, Hampe J, Nikolaus S, Nürnberg P, Krawczak M, Schürmann M, Rosenstiel P, Nebel A, and Schreiber S
Subjects: Chromosome Mapping, Colitis, Ulcerative epidemiology, Colitis, Ulcerative genetics, Crohn Disease epidemiology, Genetic Predisposition to Disease epidemiology, Genome, Human, Genotype, Humans, Odds Ratio, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Factors, Sarcoidosis epidemiology, Chromosomes, Human, Pair 10, Crohn Disease genetics, Genomics, Sarcoidosis genetics
Abstract: Background & Aims: Crohn's disease (CD) and sarcoidosis (SA) are chronic inflammatory barrier diseases that share several clinical and immunological features, including the occurrence of granulomas., Methods: A 100k genome-wide association study with 83,360 single-nucleotide polymorphisms (SNPs) was performed on 382 CD patients, 398 SA patients, and 394 control individuals. The 24 SNPs that were most strongly associated in the combined CD/SA phenotype were selected for verification in an independent sample of 1,317 patients (660 CD and 657 SA) and 1,091 controls., Results: The most significant association (Bonferroni corrected P = .036) was obtained at SNP rs1398024 on chromosome 10p12.2, with an odds ratio (OR) for both diseases of 0.81 (95% confidence interval [CI], 0.69-0.96) for carriership of the rarer allele A. The P value in the overall combined sample was 4.24 x 10(-6). During further follow-up, a moderate association (OR, 0.83; 95% CI, 0.72-0.96; P = .015) was observed between rs1398024 and ulcerative colitis (1,080 patients vs 1,091 controls), the second main subphenotype of inflammatory bowel disease in addition to CD. Extensive fine mapping of the 10p12.2 locus points to yet unidentified variants in the C10ORF67 gene region as the most likely underlying risk factors., Conclusion: Our study demonstrates that the combined analysis of different, albeit clinically related, phenotypes can lead to the identification of common susceptibility loci.
Published: 2008
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36. Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis.

Author: Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, Schuldt D, Nikolaus S, Rosenstiel P, Krawczak M, and Schreiber S
Subjects: Adult, Case-Control Studies, Cohort Studies, Colitis, Ulcerative epidemiology, Crohn Disease epidemiology, Female, Guanine Nucleotide Exchange Factors genetics, Homeodomain Proteins genetics, Humans, Male, Protein Tyrosine Phosphatase, Non-Receptor Type 2 genetics, Risk Factors, STAT3 Transcription Factor genetics, Ubiquitin-Protein Ligases, Biomarkers metabolism, Chromosomes, Human, Pair 3 genetics, Colitis, Ulcerative genetics, Crohn Disease genetics, Genetic Predisposition to Disease, Genetic Variation, Polymorphism, Single Nucleotide genetics
Abstract: Following up on recent genome-wide association studies (GWAS) of Crohn's disease, we investigated 50 previously reported susceptibility loci in a German sample of individuals with Crohn's disease (n = 1,850) or ulcerative colitis (n = 1,103) and healthy controls (n = 1,817). Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection.
Published: 2008
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37. Systematic association mapping identifies NELL1 as a novel IBD disease gene.

Author: Franke A, Hampe J, Rosenstiel P, Becker C, Wagner F, Häsler R, Little RD, Huse K, Ruether A, Balschun T, Wittig M, Elsharawy A, Mayr G, Albrecht M, Prescott NJ, Onnie CM, Fournier H, Keith T, Radelof U, Platzer M, Mathew CG, Stoll M, Krawczak M, Nürnberg P, and Schreiber S
Subjects: Calcium-Binding Proteins, Chromosome Mapping, Colitis, Ulcerative genetics, Crohn Disease genetics, Genotype, Haplotypes, Humans, Inflammatory Bowel Diseases pathology, Models, Molecular, Molecular Sequence Data, Nerve Tissue Proteins chemistry, Nerve Tissue Proteins metabolism, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Tissue Distribution, Genetic Predisposition to Disease, Genome-Wide Association Study, Inflammatory Bowel Diseases genetics, Nerve Tissue Proteins genetics
Abstract: Crohn disease (CD), a sub-entity of inflammatory bowel disease (IBD), is a complex polygenic disorder. Although recent studies have successfully identified CD-associated genetic variants, these susceptibility loci explain only a fraction of the heritability of the disease. Here, we report on a multi-stage genome-wide scan of 393 German CD cases and 399 controls. Among the 116,161 single-nucleotide polymorphisms tested, an association with the known CD susceptibility gene NOD2, the 5q31 haplotype, and the recently reported CD locus at 5p13.1 was confirmed. In addition, SNP rs1793004 in the gene encoding nel-like 1 precursor (NELL1, chromosome 11p15.1) showed a consistent disease-association in independent German population- and family-based samples (942 cases, 1082 controls, 375 trios). Subsequent fine mapping and replication in an independent sample of 454 French/Canadian CD trios supported the authenticity of the NELL1 association. Further confirmation in a large German ulcerative colitis (UC) sample indicated that NELL1 is a ubiquitous IBD susceptibility locus (combined p<10(-6); OR = 1.66, 95% CI: 1.30-2.11). The novel 5p13.1 locus was also replicated in the French/Canadian sample and in an independent UK CD patient panel (453 cases, 521 controls, combined p<10(-6) for SNP rs1992660). Several associations were replicated in at least one independent sample, point to an involvement of ITGB6 (upstream), GRM8 (downstream), OR5V1 (downstream), PPP3R2 (downstream), NM_152575 (upstream) and HNF4G (intron).
Published: 2007
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