Academic Journal
Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
| العنوان: | Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls |
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| المؤلفون: | Flannick J., Mercader J. M., Fuchsberger C., Udler M. S., Mahajan A., Wessel J., Teslovich T. M., Caulkins L., Koesterer R., Barajas-Olmos F., Blackwell T. W., Boerwinkle E., Brody J. A., Centeno-Cruz F., Chen L., Chen S., Contreras-Cubas C., Cordova E., Correa A., Cortes M., DeFronzo R. A., Dolan L., Drews K. L., Elliott A., Floyd J. S., Gabriel S., Garay-Sevilla M. E., Garcia-Ortiz H., Gross M., Han S., Heard-Costa N. L., Jackson A. U., Jorgensen M. E., Kang H. M., Kelsey M., Kim B. -J., Koistinen H. A., Kuusisto J., Leader J. B., Linneberg A., Liu C. -T., Liu J., Lyssenko V., Manning A. K., Marcketta A., Malacara-Hernandez J. M., Martinez-Hernandez A., Matsuo K., Mayer-Davis E., Mendoza-Caamal E., Mohlke K. L., Morrison A. C., Ndungu A., Ng M. C. Y., O'Dushlaine C., Payne A. J., Pihoker C., Post W. S., Preuss M., Psaty B. M., Vasan R. S., Rayner N. W., Reiner A. P., Revilla-Monsalve C., Robertson N. R., Santoro N., Schurmann C., So W. Y., Soberon X., Stringham H. M., Strom T. M., Tam C. H. T., Thameem F., Tomlinson B., Torres J. M., Tracy R. P., van Dam R. M., Vujkovic M., Wang S., Welch R. P., Witte D. R., Wong T. -Y., Atzmon G., Barzilai N., Blangero J., Bonnycastle L. L., Bowden D. W., Chambers J. C., Chan E., Cheng C. -Y., Cho Y. S., Collins F. S., de Vries P. S., Duggirala R., Glaser B., Gonzalez C., Gonzalez M. E., Groop L., Kooner J. S., Kwak S. H., Laakso M., Lehman D. M., Nilsson P., Spector T. D., Tai E. S., Tuomi T., Tuomilehto J., Wilson J. G., Aguilar-Salinas C. A., Bottinger E., Burke B., Carey D. J., Chan J. C. N., Dupuis J., Frossard P., Heckbert S. R., Hwang M. Y., Kim Y. J., Kirchner H. L., Lee J. -Y., Lee J., Loos R. J. F., Ma R. C. W., Morris A. D., O'Donnell C. J., Palmer C. N. A., Pankow J., Park K. S., Rasheed A., Saleheen D., Sim X., Small K. S., Teo Y. Y., Haiman C., Hanis C. L., Henderson B. E., Orozco L., Tusie-Luna T., Dewey F. E., Baras A., Gieger C., Meitinger T., Strauch K., Lange L., Grarup N., Hansen T., Pedersen O., Zeitler P., Dabelea D., Abecasis G., Bell G. I., Cox N. J., Seielstad M., Sladek R., Meigs J. B., Rich S. S., Rotter J. I., Altshuler D., Burtt N. P., Scott L. J., Morris A. P., Florez J. C., McCarthy M. I., Boehnke M. |
| المساهمون: | Flannick, J., Mercader, J. M., Fuchsberger, C., Udler, M. S., Mahajan, A., Wessel, J., Teslovich, T. M., Caulkins, L., Koesterer, R., Barajas-Olmos, F., Blackwell, T. W., Boerwinkle, E., Brody, J. A., Centeno-Cruz, F., Chen, L., Chen, S., Contreras-Cubas, C., Cordova, E., Correa, A., Cortes, M., Defronzo, R. A., Dolan, L., Drews, K. L., Elliott, A., Floyd, J. S., Gabriel, S., Garay-Sevilla, M. E., Garcia-Ortiz, H., Gross, M., Han, S., Heard-Costa, N. L., Jackson, A. U., Jorgensen, M. E., Kang, H. M., Kelsey, M., Kim, B. -J., Koistinen, H. A., Kuusisto, J., Leader, J. B., Linneberg, A., Liu, C. -T., Liu, J., Lyssenko, V., Manning, A. K., Marcketta, A., Malacara-Hernandez, J. M., Martinez-Hernandez, A., Matsuo, K., Mayer-Davis, E., Mendoza-Caamal, E., Mohlke, K. L., Morrison, A. C., Ndungu, A., Ng, M. C. Y., O'Dushlaine, C., Payne, A. J., Pihoker, C., Post, W. S., Preuss, M., Psaty, B. M., Vasan, R. S., Rayner, N. W., Reiner, A. P., Revilla-Monsalve, C., Robertson, N. R., Santoro, N., Schurmann, C., So, W. Y., Soberon, X., Stringham, H. M., Strom, T. M., Tam, C. H. T., Thameem, F., Tomlinson, B., Torres, J. M., Tracy, R. P., van Dam, R. M., Vujkovic, M., Wang, S., Welch, R. P., Witte, D. R., Wong, T. -Y., Atzmon, G., Barzilai, N., Blangero, J., Bonnycastle, L. L., Bowden, D. W., Chambers, J. C., Chan, E., Cheng, C. -Y., Cho, Y. S., Collins, F. S., de Vries, P. S., Duggirala, R., Glaser, B., Gonzalez, C., Gonzalez, M. E., Groop, L., Kooner, J. S., Kwak, S. H. |
| سنة النشر: | 2019 |
| المجموعة: | Università degli Studi del Molise: IRIS |
| مصطلحات موضوعية: | Animal, Case-Control Studie, Decision Support Technique, Diabetes Mellitus, Type 2, Exome, Female, Gene Frequency, Genome-Wide Association Study, Human, Male, Mice, Knockout, Whole Exome Sequencing |
| الوصف: | Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791individuals with type 2 diabetes (T2D) and 24,440non-diabetic control participants from 5ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4genes at exome-wide significance, including a series of more than 30SLC30A8 alleles that conveys protection against T2D, and in 12gene sets, including those corresponding to T2D drug targets (P=6.1×10−3) and candidate genes from knockout mice (P=5.2×10−3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000–185,000sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000470149000041; volume:570; issue:7759; firstpage:71; lastpage:76; numberofpages:6; journal:NATURE; http://hdl.handle.net/11695/90981; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85066251977; http://www.nature.com/nature/index.html |
| DOI: | 10.1038/s41586-019-1231-2 |
| الاتاحة: | http://hdl.handle.net/11695/90981 https://doi.org/10.1038/s41586-019-1231-2 http://www.nature.com/nature/index.html |
| رقم الانضمام: | edsbas.42DBAB0B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41586-019-1231-2 |
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