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5 results on '"Brown KM"'

1. Coinfection ofStreptococcus pneumoniaereduces airborne transmission of influenza virus

Author

Hiller Nl, Valerie Le Sage, Gabriella H. Padovani, Andrea J. French, Michael M. Myerburg, Brown Km, Annika J. Avery, Jason W. Rosch, Jennifer Jones, Seema S. Lakdawala, and Stacey Schultz-Cherry

Subjects
Serotype, Transmission (medicine), Biology, medicine.disease_cause, medicine.disease, Airborne transmission, Virology, Virus, medicine.anatomical_structure, Streptococcus pneumoniae, medicine, Coinfection, Viral shedding, Respiratory tract
Abstract

Secondary bacterial infection, especially withStreptococcus pneumoniae(Spn), is a common complication in fatal and ICU cases of influenza virus infection. During the H1N1 pandemic of 2009 (H1N1pdm09), there was higher mortality in healthy young adults due to secondary bacterial pneumonia, with Spn being the most frequent bacterial species. Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, we used the ferret model to study whether airborne transmission of H1N1pdm09 was influenced by coinfection with two Spn serotypes: type 2 (D39) and type 19F (BHN97). We found that coinfected animals experienced more severe clinical symptoms as well as increased bacterial colonization of the upper respiratory tract. In contrast, we observed that coinfection resulted in reduced airborne transmission of influenza virus. Only 1/3 animals coinfected with D39 transmitted H1N1pdm09 virus to a naïve recipient compared to 3/3 transmission efficiency in animals infected with influenza virus alone. A similar trend was seen in coinfection with BHN97, suggesting that coinfection with Spn reduces influenza virus airborne transmission. The decrease in transmission does not appear to be caused by decreased stability of H1N1pdm09 in expelled droplets in the presence of Spn. Rather, coinfection resulted in decreased viral shedding in the ferret upper respiratory tract. Thus, we conclude that coinfection enhances colonization and airborne transmission of Spn but decreases replication and transmission of H1N1pdm09. Our data points to an asymmetrical relationship between these two pathogens rather than a synergistic one.SignificanceAirborne transmission of respiratory viruses is influenced by many host and environmental parameters. The complex interplay between bacterial and viral coinfections on transmission of respiratory viruses has been understudied. We demonstrate that coinfection withStreptococcus pneumoniaereduces airborne transmission of influenza A viruses by decreasing viral titers in the upper respiratory tract. Instead of implicating a synergistic relationship between bacteria and virus, our work demonstrates an asymmetric relationship where bacteria benefit from the virus but where the fitness of influenza A viruses is negatively impacted by coinfection. The implications of exploring how microbial communities can influence the fitness of pathogenic organisms is a novel avenue for transmission control of pandemic respiratory viruses.

Published
2020

2. Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Author

Duffy, David L, Zhu, Gu, Xin, Li, Sanna, Marianna, Iles, Mark M, Jacobs, Leonie C, Evans, David M, Yazar, Seyhan, Beesley, Jonathan, Law, Matthew H, Kraft, Peter, Visconti, Alessia, Taylor, John C, Lui, Fan, Wright, Margaret J, Henders, Anjali K, Bowdler, Lisa, Glass, Dan, Ikram, Arfan M, Uitterlinden, André G, Madden, Pamela A, Heath, Andrew C, Nelson, Elliot C, Green, Adele C, Chanock, Stephen, Barrett, Jennifer H, Brown, Matthew A, Hayward, Nicholas K, Macgregor, Stuart, Sturm, Richard A, Hewitt, Alex W, Kayser, Manfred, Hunter, David J, Newton Bishop, Julia A, Spector, Timothy D, Montgomery, Grant W, Mackey, David A, Smith, George Davey, Nijsten, Tamar E, Bishop, D Timothy, Bataille, Veronique, Falchi, Mario, Han, Jiali, Martin, Nicholas, G, Lee, Je, Brossard, M, Moses, Ek, Song, F, Kumar, R, Easton, Df, Pharoah, Pdp, Swerdlow, Aj, Kypreou, Kp, Harland, M, Randerson-Moor, J, Akslen, La, Andresen, Pa, Avril, Mf, Azizi, E, Scarrà, Gb, Brown, Km, Dębniak, T, Elder, De, Fang, S, Friedman, E, Galan, P, Ghiorzo, P, Gillanders, Em, Goldstein, Am, Gruis, Na, Hansson, J, Helsing, P, Hočevar, M, Höiom, V, Ingvar, C, Kanetsky, Pa, Chen, Wv, Landi, Mt, Lang, J, Lathrop, Gm, Lubiński, J, Mackie, Rm, Mann, Gj, Molven, A, Novaković, S, Olsson, H, Puig, S, Puig-Butille, Ja, Radford-Smith, Gl, van der Stoep, N, van Doorn, R, Whiteman, Dc, Craig, Je, Schadendorf, D, Simms, La, Burdon, Kp, Nyholt, Dr, Pooley, Ka, Orr, N, Stratigos, Aj, Cust, Ae, Ward, Sv, Schulze, Hj, Dunning, Am, Demenais, F, Amos, Ci., Apollo - University of Cambridge Repository, Dermatology, Genetic Identification, Epidemiology, Internal Medicine, and Consortium, Melanoma Gwas

Subjects
0301 basic medicine, Skin Neoplasms, Medizin, General Physics and Astronomy, Genome-wide association study, Receptors, G-Protein-Coupled, 0302 clinical medicine, Guanine Nucleotide Exchange Factors, lcsh:Science, skin and connective tissue diseases, Melanoma, Telomerase, Genetics, 0303 health sciences, Nevus, Pigmented, Stem Cell Factor, Multidisciplinary, Microfilament Proteins, Nuclear Proteins, RNA-Binding Proteins, Genetic Pleiotropy, Microphthalmia-associated transcription factor, 3. Good health, 030220 oncology & carcinogenesis, Cytochrome P-450 CYP1B1, Interferon Regulatory Factors, Medical genetics, PPARGC1B, Dock8, medicine.medical_specialty, Science, Telomere-Binding Proteins, Single-nucleotide polymorphism, Nerve Tissue Proteins, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Histone Deacetylases, White People, Group VI Phospholipases A2, 03 medical and health sciences, Genetic predisposition, Pigmented Nevus, medicine, Nevus, Humans, Genetic Predisposition to Disease, neoplasms, 030304 developmental biology, General Chemistry, medicine.disease, Repressor Proteins, MicroRNAs, 030104 developmental biology, Cutaneous melanoma, RNA, lcsh:Q, Carrier Proteins, IRF4, Genome-Wide Association Study
Abstract

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, United Kingdom, and United States, comprising a total of 52,506 phenotyped individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs at a genome-wide level of significance in KITLG, DOCK8, and a broad region of 9q32. In a bivariate analysis combining the nevus results with those from a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level of significance. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis via genes we can show to be expressed under control of the MITF melanocytic cell lineage regulator.

Published
2018

3. Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

Author

Fang, J, Jia, J, Makowski, M, Xu, M, Wang, Z, Zhang, T, Hoskins, Jw, Choi, J, Han, Y, Zhang, M, Thomas, J, Kovacs, M, Collins, I, Dzyadyk, M, Thompson, A, O'Neill, M, Das, S, Lan, Q, Koster, R, Solomon, Rs, Kraft, P, Wolpin, Bm, Jansen, Pwtc, Olson, S, Mcglynn, Ka, Kanetsky, Pa, Chatterjee, N, Barrett, Jh, Dunning, Am, Taylor, Jc, Newton Bishop, Ja, Bishop, Dt, Andresson, T, Petersen, Gm, Amos, Ci, Iles, Mm, Nathanson, Kl, Landi, Mt, Vermeulen, M, Brown, Km, Amundadottir, Lt, Canzian, F, Kooperberg, C, Arslan, Aa, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Jacobs, Ej, Kamineni, A, Van Den Eeden, S, Klein, Ap, Kolonel, Ln, Li, D, Olson, Sh, Risch, Ha, Sesso, Hd, Visvanathan, K, Zheng, W, Albanes, D, Austin, Ma, Boutron Ruault, Mc, Bueno de Mesquita, Hb, Cotterchio, M, Gaziano, Jm, Giovannucci, El, Goggins, M, Gross, M, Hassan, M, Helzlsouer, Kj, Holly, Ea, Hunter, Dj, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Krogh, V, Kurtz, Rc, Lacroix, A, Le Marchand, L, Mannisto, S, Patel, Av, Peeters, Phm, Riboli, E, Shu, Xo, Sund, M, Thornquist, M, Tjønneland, A, Tobias, Gs, Trichopoulos, D, Wactawski Wende, J, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Hoover, R, Hartge, P, Fuchs, C, Chanock, Sj, Stevens, V, Caporaso, Ne, Brennan, P, Mckay, J, Wu, X, Hung, Rj, Mclaughlin, Jr, Bickeboller, H, Risch, A, Wichmann, E, Houlston, R, Mann, G, Hopper, J, Aitken, J, Armstrong, B, Giles, G, Holland, E, Kefford, R, Cust, A, Jenkins, M, Schmid, H, Puig, S, Aguilera, P, Badenas, C, Barreiro, A, Carrera, C, Gabriel, D, Xavier, Pg, Iglesias Garcia, P, Malvehy, J, Mila, M, Pigem, R, Potrony, M, Batille, Ja, Marti, Gt, Hayward, N, Martin, N, Montgomery, G, Duffy, D, Whiteman, D, Gregor, Sm, Calista, D, Landi, G, Minghetti, P, Arcangeli, F, Bertazzi, Pa, Ghiorzo, Paola, Bianchi, Giovanna, Pastorino, Lorenza, Bruno, William, Andreotti, Virginia, Queirolo, P, Spagnolo, Francesco, Mackie, R, Lang, J, Gruis, N, van Nieuwpoort, Fa, Out, C, Bergman, W, Kukutsch, N, Bavinck, Jnb, Bakker, B, van der Stoep, N, Ter Huurne, J, van der Rhee, H, Bekkenk, M, Snels, D, van Praag, M, Brochez, L, Gerritsen, R, Crijns, M, Vasen, H, Janssen, B, Ingvar, C, Olsson, H, Jonsson, G, Borg, A, Harbst, K, Nielsen, K, Zander, As, Molvern, A, Helsing, P, Andresen, Pa, Rootwelt, H, Akslen, La, Bressac de Paillerets, B, Demenais, F, Avril, Mf, Chaudru, V, Jeannin, P, Lesueur, F, Maubec, E, Mohamdi, H, Bossard, M, Vaysse, A, Boitier, F, Caron, O, Caux, F, Dalle, S, Dereure, O, Leroux, D, Martin, L, Mateus, C, Robert, C, Stoppa Lyonnet, D, Thomas, L, Wierzbicka, E, Elder, D, Ming, M, Mitra, N, Debniak, T, Lubinski, J, Hocevar, M, Novakovic, S, Peric, B, Skerl, P, Hansson, J, Hoiom, V, Freidman, E, Azizi, E, Baron Epel, O, Scope, A, Pavlotsky, F, Cohen Manheim, I, Laitman, Y, Harland, M, Randerson Moor, J, Laye, J, Davies, J, Nsengimana, J, O'Shea, S, Chan, M, Gascoyne, J, Tucker, Ma, Goldstein, Am, and Yang, X. r.

Subjects
0301 basic medicine, Male, Lung Neoplasms, Skin Neoplasms, General Physics and Astronomy, Genome-wide association study, VARIANTS, Histones, Skin cancer, RNA, Small Interfering, Melanoma, Telomerase, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Pancreas cancer, Regulation of gene expression, Genetics, Zinc finger, Gene knockdown, Multidisciplinary, Proteomics and Chromatin Biology, TRICL Consortium, Chromosome Mapping, GenoMEL Consortium, PANCREATIC-CANCER, Multidisciplinary Sciences, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Science & Technology - Other Topics, Chromosomes, Human, Pair 5, Female, Lung cancer, Signal Transduction, SUSCEPTIBILITY LOCI, Science, Locus (genetics), Single-nucleotide polymorphism, PROMOTES GROWTH, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, LUNG-CANCER, Testicular Neoplasms, Cell Line, Tumor, MD Multidisciplinary, Humans, Genetic Predisposition to Disease, QUANTITATIVE PROTEOMICS, GENOME-WIDE ASSOCIATION, Gene, PanScan Consortium, Càncer de pell, Càncer de pàncrees, Alleles, Science & Technology, Kirurgi, HUMAN-CELLS, Telomere Homeostasis, Correction, General Chemistry, Molecular biology, TERT-CLPTM1L LOCUS, Telomere, Pancreatic Neoplasms, 030104 developmental biology, Genetic Loci, TELOMERE LENGTH, Càncer de pulmó, Surgery, Genètica, Genome-Wide Association Study, Transcription Factors
Abstract

Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele., Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

Published
2017

4. Genome-wide association study identifies novel loci predisposing to cutaneous melanoma†

Author

Amos, Ci, Wang, Le, Lee, Je, Gershenwald, Je, Chen, Wv, Fang, S, Kosoy, R, Zhang, M, Qureshi, Aa, Vattathil, S, Schacherer, Cw, Gardner, Jm, Wang, Y, Bishop, Dt, Barrett, Jh, Macgregor, S, Hayward, Nk, Martin, Ng, Duffy, Dl, Mann, Gj, Cust, A, Hopper, J, Brown, Km, Grimm, Ea, Xu, Y, Han, Y, Jing, K, Mchugh, C, Laurie, Cc, Doheny, Kf, Pugh, Ew, Seldin, Mf, Han, J, Wei, Q, Genomel, Investigators, Mega Investigators, Q., AMFS Investigators Mann GJ, Hopper, Jl, Aitken, Jf, Armstrong, Bk, Giles, Gg, Kefford, Rf, Cust, Ae, Jenkins, Ma, Schmid, H, Aguilera, P, Badenas, C, Carrera, C, Cuellar, F, Gabriel, D, Martinez, E, Gonzalez, M, Iglesias, P, Malvehy, J, Marti Laborda, R, Mila, M, Ogbah, Z, Butille, Ja, Puig, S, Alós, L, Arance, A, Arguís, P, Campo, A, Castel, T, Conill, C, Palou, J, Rull, R, Sánchez, M, Vidal Sicart, S, Vilalta, A, Vilella, R, Montgomery, Gw, Whiteman, Dc, Whiteman, D, Webb, P, Green, A, Parsons, P, Purdie, D, Hayward, N, Landi, Mt, Calista, D, Landi, G, Minghetti, P, Arcangeli, F, Bertazzi, Pa, Bianchi, Giovanna, Ghiorzo, Paola, Pastorino, Lorenza, Bruno, William, Battistuzzi, Linda, Gargiulo, Sara, Nasti, Sabina, Gliori, S, Origone, Paola, Andreotti, V, Queirolo, P, Mackie, R, Lang, J, Bishop, Ja, Affleck, P, Harrison, J, Iles, Mm, Randerson Moor, J, Harland, M, Taylor, Jc, Whittaker, L, Kukalizch, K, Leake, S, Karpavicius, B, Haynes, S, Mack, T, Chan, M, Taylor, Y, Davies, J, King, P, Gruis, Na, van Nieuwpoort FA, Out, C, van der Drift, C, Bergman, W, Kukutsch, N, Bavinck, Jn, Bakker, B, van der Stoep, N, ter Huurne, J, van der Rhee, H, Bekkenk, M, Snels, D, van Praag, M, Brochez, L, Gerritsen, R, Crijns, M, Vasen, H, Olsson, H, Ingvar, C, Jönsson, G, Borg, Å, Måsbäck, A, Lundgren, L, Baeckenhorn, K, Nielsen, K, Casslén, As, Helsing, P, Andresen, Pa, Rootwelt, H, Akslen, La, Molven, A, Avril, Mf, Bressac de Paillerets, B, Chaudru, V, Chateigner, N, Corda, E, Jeannin, P, Lesueur, F, de Lichy, M, Maubec, E, Mohamdi, H, Demenais, F, Andry Benzaquen, P, Bachollet, B, Bérard, F, Berthet, P, Boitier, F, Bonadona, V, Bonafé, Jl, Bonnetblanc, Jm, Cambazard, F, Caron, O, Caux, F, Chevrant Breton, J, Chompret, A, Dalle, S, Demange, L, Dereure, O, Doré, Mx, Doutre, Ms, Dugast, C, Faivre, L, Grange, F, Humbert, P, Joly, P, Kerob, D, Lasset, C, Leccia, Mt, Lenoir, G, Leroux, D, Levang, J, Lipsker, D, Mansard, S, Martin, L, Martin Denavit, T, Mateus, C, Michel, Jl, Morel, P, Olivier Faivre, L, Perrot, Jl, Robert, C, Ronger Savle, S, Sassolas, B, Souteyrand, P, Stoppa Lyonnet, D, Thomas, L, Vabres, P, Wierzbicka, E, Elder, D, Kanetsky, P, Knorr, J, Ming, M, Mitra, N, Ruffin, A, Van Belle, P, Debniak, T, Lubiński, J, Mirecka, A, Ertmański, S, Novakovic, S, Hocevar, M, Peric, B, Cerkovnik, P, Höiom, V, Hansson, J, Holland, Ea, Azizi, E, Galore Haskel, G, Friedman, E, Baron Epel, O, Scope, A, Pavlotsky, F, Yakobson, E, Cohen Manheim, I, Laitman, Y, Milgrom, R, Shimoni, I, and Kozlovaa, E.

Subjects
Genetic Markers, Candidate gene, Skin Neoplasms, Ubiquitin-Protein Ligases, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Genetics, Eye color, Guanine Nucleotide Exchange Factors, Humans, SNP, Genetic Predisposition to Disease, Melanoma, Molecular Biology, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Pigmentation, Association Studies Articles, General Medicine, 3. Good health, Chromosomes, Human, Pair 1, Genetic Loci, Genetic marker, Case-Control Studies, 030220 oncology & carcinogenesis, Cutaneous melanoma, Genome-Wide Association Study
Abstract

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

Published
2011

5. Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

Author

Law, M, Bishop, DT, Lee, JE, Brossard, M, Martin, NG, Moses, EK, Song, F, Barrett, JH, Kumar, R, Easton, DF, Pharoah, PDP, Swerdlow, AJ, Kypreou, KP, Taylor, JC, Harland, M, Randerson-Moor, J, Akslen, LA, Andresen, PA, Avril, MF, Azizi, E, Scarra, GB, Brown, KM, Debniak, T, Duffy, DL, Elder, DE, Fang, S, Friedman, E, Galan, P, Ghiorzo, P, Gillanders, EM, Goldstein, AM, Gruis, NE, Hansson, J, Helsing, P, Hocevar, M, Hoiom, V, Ingvar, C, Kanetsky, PA, Chen, WV, GenoMEL Consortium, Essen-Heidelberg Investigators, The SDH Study Group, Q-MEGA and QTWIN Investigators, AMFS Investigators, ATHENS Melanoma Study Group, Landi, MT, Lang, J, Lathrop, M, Lubinski, J, Mackie, RM, Mann, GJ, Molvern, A, Montgomery, GW, Novakovic, S, Olsson, H, Puig, S, Puig-Butille, JA, Qureshi, AA, Radford-Smith, GL, van der Stoep, N, van Doorn, R, Whiteman, DC, Craig, JE, Schadendorf, D, Simms, LA, Burdon, KP, Nyholt, DR, Pooley, KA, Orr, N, Stratigos, AJ, Cust, AE, Ward, SV, Hayward, NK, Han, J, Schulze, HJ, Dunning, AM, Newton-Bishop, JA, Demenais, F, Amos, CI, MacGregor, S, Iles, MM, Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Pooley, Karen [0000-0002-1274-9460], Dunning, Alison [0000-0001-6651-7166], and Apollo - University of Cambridge Repository

Subjects
Candidate gene, Skin Neoplasms, Medizin, Single-nucleotide polymorphism, Genome-wide association study, Biology, Genome, Polymorphism, Single Nucleotide, Article, Polymorphism (computer science), ATHENS Melanoma Study Group, Genetics, Chromosomes, Human, Humans, Genetic Predisposition to Disease, AMFS Investigators, Melanoma, Genetic association, 11 Medical And Health Sciences, 06 Biological Sciences, GenoMEL Consortium, Human genetics, 3. Good health, Genetic Loci, Case-Control Studies, SDH Study Group, Expression quantitative trait loci, Q-MEGA and QTWIN Investigators, Essen-Heidelberg Investigators, Developmental Biology, Genome-Wide Association Study
Abstract

© 2015 Nature America, Inc. All rights reserved.Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10-8), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

Published
2015

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