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      Identification of nine new susceptibility loci for endometrial cancer

      research-article
      1 , , 1 , 2 , 2 , 3 , 4 , 5 , 3 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 14 , 15 , 16 , 10 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 10 , 25 , 26 , 27 , 28 , 17 , 20 , 29 , 30 , 31 , 32 , 26 , 33 , 34 , 35 , 11 , 2 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 9 , 43 , 44 , 30 , 45 , 46 , 10 , 47 , 48 , 18 , 49 , 50 , 51 , 27 , 52 , 34 , 53 , 33 , 54 , 55 , 9 , 39 , 56 , 57 , 58 , 3 , 6 , 18 , 26 , 59 , 27 , 57 , 58 , 60 , 61 , 62 , 37 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 6 , 72 , 11 , 73 , 18 , 49 , 74 , 1 , 46 , 75 , 76 , 65 , 77 , 27 , 35 , 78 , 52 , 33 , 77 , 79 , 80 , 69 , 81 , 82 , 41 , 83 , 84 , 85 , 86 , 3 , 4 , 5 , 87 , 52 , 55 , 52 , 68 , 17 , 88 , 89 , 90 , 66 , 91 , 57 , 58 , 26 , 55 , 92 , 52 , 93 , 10 , 94 , 10 , 57 , 58 , 95 , 96 , 52 , 97 , 10 , 64 , 68 , 11 , 55 , 55 , 26 , 59 , 26 , 33 , 27 , 71 , 11 , 55 , 1 , , 11 ,
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          Abstract

          Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins ( SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

          Abstract

          Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

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          Most cited references27

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          Type I and II endometrial cancers: have they different risk factors?

          Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m(2) increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.
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            Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

            John Perry, Ken Ong and colleagues analyze genotype data on ∼370,000 women and identify 389 independent signals that associate with age at menarche, implicating ∼250 genes. Their analyses suggest causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men.
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              Chromosomal passengers: conducting cell division.

              Mitosis and meiosis are remarkable processes during which cells undergo profound changes in their structure and physiology. These events are orchestrated with a precision that is worthy of a classical symphony, with different activities being switched on and off at precise times and locations throughout the cell. One essential 'conductor' of this symphony is the chromosomal passenger complex (CPC), which comprises Aurora-B protein kinase, the inner centromere protein INCENP, survivin and borealin (also known as Dasra-B). Studies of the CPC are providing insights into its functions, which range from chromosome-microtubule interactions to sister chromatid cohesion to cytokinesis, and constitute one of the most dynamic areas of ongoing mitosis and meiosis research.
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                Author and article information

                Contributors
                Tracy.OMara@qimrberghofer.edu.au
                Amanda.Spurdle@qimrberghofer.edu.au
                djt25@medschl.cam.ac.uk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                9 August 2018
                9 August 2018
                2018
                : 9
                : 3166
                Affiliations
                [1 ]ISNI 0000 0001 2294 1395, GRID grid.1049.c, Department of Genetics and Computational Biology, , QIMR Berghofer Medical Research Institute, ; Brisbane, 4006 QLD Australia
                [2 ]Department of Obstetrics and Gynecology, University Hospitals KU Leuven, University of Leuven, Division of Gynecologic Oncology, Leuven, 3000 Belgium
                [3 ]ISNI 0000 0004 0577 6676, GRID grid.414724.0, John Hunter Hospital, Hunter Medical Research Institute, ; Newcastle, 2305 NSW Australia
                [4 ]ISNI 0000 0000 8831 109X, GRID grid.266842.c, University of Newcastle, Centre for Information Based Medicine, ; Callaghan, 2308 NSW Australia
                [5 ]ISNI 0000 0000 8831 109X, GRID grid.266842.c, University of Newcastle, Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, ; Callaghan, 2308 NSW Australia
                [6 ]ISNI 0000 0000 8831 109X, GRID grid.266842.c, University of Newcastle, Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, ; Callaghan, 2308 NSW Australia
                [7 ]ISNI 0000 0001 2180 1622, GRID grid.270240.3, Cancer Prevention Program, , Fred Hutchinson Cancer Research Center, ; Seattle, 98109 WA USA
                [8 ]ISNI 0000 0001 0695 7223, GRID grid.267468.9, University of Wisconsin-Milwaukee, Zilber School of Public Health, ; Milwaukee, 53205 WI USA
                [9 ]Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center ER-EMN, Erlangen, 91054 Germany
                [10 ]ISNI 0000 0004 1936 8075, GRID grid.48336.3a, National Cancer Institute, Division of Cancer Epidemiology and Genetics, ; Bethesda, 20892 MD USA
                [11 ]ISNI 0000000121885934, GRID grid.5335.0, Department of Public Health and Primary Care, , University of Cambridge, Centre for Cancer Genetic Epidemiology, ; Cambridge, CB1 8RN UK
                [12 ]ISNI 0000 0004 0564 2483, GRID grid.418579.6, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, ; Stuttgart, 70376 Germany
                [13 ]ISNI 0000 0001 2190 1447, GRID grid.10392.39, University of Tübingen, ; Tübingen, 72074 Germany
                [14 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), ; Heidelberg, 69120 Germany
                [15 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, Division of Clinical Epidemiology and Aging Research, , German Cancer Research Center (DKFZ), ; Heidelberg, 69120 Germany
                [16 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, Division of Preventive Oncology, , German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), ; Heidelberg, 69120 Germany
                [17 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Clinical Pathology, , The University of Melbourne, ; Melbourne, 3010 VIC Australia
                [18 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, ; Melbourne, 3010 VIC Australia
                [19 ]ISNI 0000 0004 0624 1200, GRID grid.416153.4, Genetic Medicine and Family Cancer Clinic, , Royal Melbourne Hospital, ; Parkville, 3010 VIC Australia
                [20 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Victorian Comprehensive Cancer Centre, , University of Melbourne Centre for Cancer Research, ; Parkville, 3010 VIC Australia
                [21 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Department of Obstetrics and Gynecology, , University of Heidelberg, ; Heidelberg, 69120 Germany
                [22 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, Molecular Epidemiology Group, C080, , German Cancer Research Center (DKFZ), ; Heidelberg, 69120 Germany
                [23 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, Division of Cancer Epidemiology, , German Cancer Research Center (DKFZ), ; Heidelberg, 69120 Germany
                [24 ]GRID grid.412315.0, University Medical Center Hamburg-Eppendorf, Cancer Epidemiology, University Cancer Center Hamburg (UCCH), ; Hamburg, 20246 Germany
                [25 ]ISNI 0000 0001 2180 1622, GRID grid.270240.3, Epidemiology Program, , Fred Hutchinson Cancer Research Center, ; Seattle, 98109 WA USA
                [26 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Epidemiology, , Harvard T.H. Chan School of Public Health, ; Boston, 02115 MA USA
                [27 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, ; Oxford, OX3 7BN UK
                [28 ]ISNI 0000 0004 1936 834X, GRID grid.1013.3, University of Sydney, Westmead Institute for Medical Research, ; Sydney, 2145 NSW Australia
                [29 ]ISNI 0000 0001 2188 8502, GRID grid.266832.b, University of New Mexico, University of New Mexico Health Sciences Center, ; Albuquerque, 87131 NM USA
                [30 ]ISNI 0000 0001 0693 8815, GRID grid.413574.0, Department of Cancer Epidemiology and Prevention Research, , Alberta Health Services, ; Calgary, T2N 4N2 AB Canada
                [31 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Laboratory Medicine and Pathology, , Mayo Clinic, ; Rochester, 55905 MN USA
                [32 ]ISNI 0000 0004 1936 9262, GRID grid.11835.3e, Department of Oncology and Metabolism, , University of Sheffield, Sheffield Institute for Nucleic Acids (SInFoNiA), ; Sheffield, S10 2TN UK
                [33 ]Department of Medicine, Harvard Medical School, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, 02115 MA USA
                [34 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Medical Epidemiology and Biostatistics, , Karolinska Institutet, ; Stockholm, 171 65 Sweden
                [35 ]ISNI 0000000121885934, GRID grid.5335.0, University of Cambridge, MRC Epidemiology Unit, School of Clinical Medicine, ; Cambridge, CB2 0QQ UK
                [36 ]ISNI 0000000104788040, GRID grid.11486.3a, VIB, Vesalius Research Center, ; Leuven, 3000 Belgium
                [37 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Department of Human Genetics, , University of Leuven, Laboratory for Translational Genetics, ; Leuven, 3000 Belgium
                [38 ]ISNI 0000 0001 2193 0096, GRID grid.223827.e, Cancer Research Huntsman Cancer Institute Department of Population Health Sciences, , University of Utah, ; Salt Lake City, 84112 UT USA
                [39 ]ISNI 0000 0000 9529 9877, GRID grid.10423.34, Gynaecology Research Unit, , Hannover Medical School, ; Hannover, 30625 Germany
                [40 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Obstetrics and Gynecology, , Mayo Clinic, Division of Gynecologic Oncology, ; Rochester, 55905 MN USA
                [41 ]Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, 07743 Germany
                [42 ]Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Institute of Human Genetics, University Hospital Erlangen, Erlangen, 91054 Germany
                [43 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Department of Medicine, , University of California at Los Angeles, David Geffen School of Medicine, Division of Hematology and Oncology, ; Los Angeles, 90095 CA USA
                [44 ]ISNI 0000 0001 2177 6375, GRID grid.412016.0, Department of Biostatistics, , Kansas University Medical Center, ; Kansas City, 66160 KS USA
                [45 ]ISNI 0000 0004 0375 4078, GRID grid.1032.0, Curtin University, School of Public Health, ; Perth, 6102 WA Australia
                [46 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, University of Queensland, Institute for Molecular Bioscience, ; Brisbane, 4072 QLD Australia
                [47 ]Institute of Cancer Research, Division of Genetics and Epidemiology, London, SM2 5NG UK
                [48 ]American Cancer Society, Epidemiology Research Program, Atlanta, 30303 GA USA
                [49 ]ISNI 0000 0001 1482 3639, GRID grid.3263.4, Cancer Epidemiology and Intelligence Division, , Cancer Council Victoria, ; Melbourne, 3004 VIC Australia
                [50 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, Department of Epidemiology and Preventive Medicine, , Monash University, ; Melbourne, 3004 VIC Australia
                [51 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Health Science Research, , Mayo Clinic, Division of Epidemiology, ; Rochester, 55905 MN USA
                [52 ]ISNI 0000 0001 2156 6853, GRID grid.42505.36, Department of Preventive Medicine, , University of Southern California, Keck School of Medicine, ; Los Angeles, 90033 CA USA
                [53 ]Department of Oncology, South General Hospital, Stockholm, 118 83 Sweden
                [54 ]ISNI 0000 0001 2184 9220, GRID grid.266683.f, Department of Biostatistics and Epidemiology, , University of Massachusetts, Amherst, ; Amherst, 01003 MA USA
                [55 ]ISNI 0000000121885934, GRID grid.5335.0, Department of Oncology, , University of Cambridge, Centre for Cancer Genetic Epidemiology, ; Cambridge, CB1 8RN UK
                [56 ]GRID grid.264200.2, Department of Clinical Genetics, , St George’s, University of London, ; London, SW17 0RE UK
                [57 ]ISNI 0000 0004 1936 7443, GRID grid.7914.b, Department of Clinical Science, , University of Bergen, Centre for Cancer Biomarkers, ; Bergen, 5020 Norway
                [58 ]ISNI 0000 0000 9753 1393, GRID grid.412008.f, Department of Gynecology and Obstetrics, , Haukeland University Hospital, ; Bergen, 5021 Norway
                [59 ]ISNI 000000041936754X, GRID grid.38142.3c, Program in Genetic Epidemiology and Statistical Genetics, , Harvard T.H. Chan School of Public Health, ; Boston, 02115 MA USA
                [60 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Department of Cancer Genetics, , Oslo University Hospital, Radiumhospitalet, Institute for Cancer Research, ; Oslo, 0379 Norway
                [61 ]University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo, 0450 Norway
                [62 ]Department of Clinical Molecular Biology, University of Oslo, Oslo University Hospital, Oslo, 0450 Norway
                [63 ]ISNI 0000000104788040, GRID grid.11486.3a, VIB, VIB Center for Cancer Biology, ; Leuven, 3001 Belgium
                [64 ]ISNI 0000 0001 2188 0957, GRID grid.410445.0, Epidemiology Program, , University of Hawaii Cancer Center, ; Honolulu, 96813 HI USA
                [65 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Department of Epidemiology and Biostatistics, , Memorial Sloan-Kettering Cancer Center, ; New York, 10065 NY USA
                [66 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Molecular Medicine and Surgery, , Karolinska Institutet, ; Stockholm, 171 76 Sweden
                [67 ]Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center-Oncology Institute, Warsaw, 02-034 Poland
                [68 ]Department of Medicine, Vanderbilt University School of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, 37232 TN USA
                [69 ]ISNI 0000000419368710, GRID grid.47100.32, Chronic Disease Epidemiology, , Yale School of Public Health, ; New Haven, 06510 CT USA
                [70 ]ISNI 0000 0000 9891 5233, GRID grid.468198.a, Department of Anatomic Pathology, , Moffitt Cancer Center and Research Institute, ; Tampa, 33612 FL USA
                [71 ]ISNI 0000 0004 1936 7486, GRID grid.6572.6, University of Birmingham, Institute of Cancer and Genomic Sciences, ; Birmingham, B15 2TT UK
                [72 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Department of Gynecology and Obstetrics, , Ludwig-Maximilians University of Munich, ; Munich, 80336 Germany
                [73 ]ISNI 0000 0004 0609 0940, GRID grid.417705.0, Department of Electron Microscopy/Molecular Pathology, , The Cyprus Institute of Neurology and Genetics, ; Nicosia, Cyprus
                [74 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Women’s and Children’s Health, , Karolinska Institutet, ; Stockholm, 171 76 Sweden
                [75 ]ISNI 0000 0004 1936 9684, GRID grid.27860.3b, Department of Biochemistry and Molecular Medicine, , University of California Davis, ; Davis, 95817 CA USA
                [76 ]ISNI 0000 0001 0930 2361, GRID grid.4514.4, Department of Cancer Epidemiology, Clinical Sciences, , Lund University, ; Lund, 222 42 Sweden
                [77 ]ISNI 0000 0000 8831 109X, GRID grid.266842.c, University of Newcastle, School of Medicine and Public Health, ; Callaghan, 2308 NSW Australia
                [78 ]ISNI 0000 0004 0425 469X, GRID grid.8991.9, Department of Non-Communicable Disease Epidemiology, , London School of Hygiene and Tropical Medicine, ; London, WC1E 7HT UK
                [79 ]ISNI 000000041936754X, GRID grid.38142.3c, Harvard T.H. Chan School of Public Health, ; Boston, 02115 MA USA
                [80 ]ISNI 0000 0001 2106 9910, GRID grid.65499.37, Dana-Farber Cancer Institute, ; Boston, 02115 MA USA
                [81 ]Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women’s Hospital, Gynaecology Research Centre, Parkville, 3052 VIC Australia
                [82 ]Department of Gynaecology and Obstetrics, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Erlangen, 91054 Germany
                [83 ]Center for Cancer Prevention (CPO-Peimonte), Turin, 10126 Italy
                [84 ]ISNI 0000 0004 1784 6598, GRID grid.428948.b, Human Genetics Foundation (HuGeF), ; Turino, 10126 Italy
                [85 ]ISNI 0000 0001 2167 3675, GRID grid.14003.36, Department of Obstetrics and Gynecology, , University of Wisconsin, School of Medicine and Public Health, ; Madison, 53715 WI USA
                [86 ]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Department of Epidemiology and Biostatistics, , Case Western Reserve University, ; Cleveland, 44106 OH USA
                [87 ]ISNI 0000 0004 0577 6676, GRID grid.414724.0, John Hunter Hospital, Division of Molecular Medicine, Pathology North, ; Newcastle, 2308 NSW Australia
                [88 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, ; Clayton, 3168 VIC Australia
                [89 ]ISNI 0000 0001 1271 4623, GRID grid.18886.3f, Division of Genetics and Epidemiology, , The Institute of Cancer Research, ; London, SM2 5NG UK
                [90 ]ISNI 0000 0001 1271 4623, GRID grid.18886.3f, Division of Breast Cancer Research, , The Institute of Cancer Research, ; London, SW7 3RP UK
                [91 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Karolinska Institutet, Clinical Genetics, ; Stockholm, 171 76 Sweden
                [92 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Health Sciences Research, , Mayo Clinic, ; Rochester, 55905 MN USA
                [93 ]ISNI 0000 0004 0626 3338, GRID grid.410569.f, Department of Obstetrics and Gynaecology, , University Hospitals Leuven, Division of Gynecologic Oncology, Leuven Cancer Institute, ; Leuven, 3000 Belgium
                [94 ]ISNI 0000 0001 2294 1395, GRID grid.1049.c, Department of Population Health, , QIMR Berghofer Medical Research Institute, ; Brisbane, 4006 QLD Australia
                [95 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Health Science Research, , Mayo Clinic, Division of Biomedical Statistics and Informatics, ; Rochester, 55905 MN USA
                [96 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Environmental Medicine, , Karolinska Institutet, Division of Nutritional Epidemiology, ; Stockholm, 171 77 Sweden
                [97 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Epidemiology, , Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, State Key Laboratory of Oncogene and Related Genes, ; Shanghai, China
                Author information
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                http://orcid.org/0000-0002-2184-7708
                http://orcid.org/0000-0001-8413-7669
                http://orcid.org/0000-0001-9800-1308
                http://orcid.org/0000-0001-7531-2736
                http://orcid.org/0000-0003-2225-6675
                http://orcid.org/0000-0003-3789-7651
                http://orcid.org/0000-0003-4591-1214
                http://orcid.org/0000-0003-4885-8471
                http://orcid.org/0000-0002-4783-1966
                http://orcid.org/0000-0003-2601-3398
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                http://orcid.org/0000-0001-5764-7268
                http://orcid.org/0000-0002-4140-8139
                http://orcid.org/0000-0003-0733-5930
                http://orcid.org/0000-0001-7387-6845
                http://orcid.org/0000-0003-3950-4815
                http://orcid.org/0000-0003-1226-070X
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                http://orcid.org/0000-0003-1465-5799
                Article
                5427
                10.1038/s41467-018-05427-7
                6085317
                30093612
                eb0bed60-8e37-4c49-85ba-5e5757d26246
                © The Author(s) 2018

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                : 25 December 2017
                : 2 July 2018
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