دورية أكاديمية
Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity.
| العنوان: | Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity. |
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| المؤلفون: | Yaghootkar, H., Zhang, Y., Spracklen, C.N., Karaderi, T., Huang, L.O., Bradfield, J.P., Schurmann, C., Fine, R.S., Preuss, M.H., Kutalik, Z., Wittemans, L.B.L., Lu, Y., Metz, S., Willems, S.M., Li-Gao, R., Grarup, N., Wang, S., Molnos, S., Sandoval-Zárate, A.A., Nalls, M.A., Lange, L.A., Haesser, J., Guo, X., Lyytikäinen, L.P., Feitosa, M.F., Sitlani, C.M., Venturini, C., Mahajan, A., Kacprowski, T., Wang, C.A., Chasman, D.I., Amin, N., Broer, L., Robertson, N., Young, K.L., Allison, M., Auer, P.L., Blüher, M., Borja, J.B., Bork-Jensen, J., Carrasquilla, G.D., Christofidou, P., Demirkan, A., Doege, C.A., Garcia, M.E., Graff, M., Guo, K., Hakonarson, H., Hong, J., Chen, Y.D.I., Jackson, R., Jakupović, H., Jousilahti, P., Justice, A.E., Kähönen, M., Kizer, J.R., Kriebel, J., LeDuc, C.A., Li, J., Lind, L., Luan, J., Mackey, D.A., Mangino, M., Männistö, S., Carli, J.F.M., Medina-Gomez, C., Mook-Kanamori, D.O., Morris, A.P., de Mutsert, R., Nauck, M., Prokic, I., Pennell, C.E., Pradhan, A.D., Psaty, B.M., Raitakari, O.T., Scott, R.A., Skaaby, T., Strauch, K., Taylor, K.D., Teumer, A., Uitterlinden, A.G., Wu, Y., Yao, J., Walker, M., North, K.E., Kovacs, P., Ikram, M.A., van Duijn, C.M., Ridker, P.M., Lye, S.J., Homuth, G., Ingelsson, E., Spector, T.D., McKnight, B., Province, M.A., Lehtimäki, T., Adair, L.S., Rotter, J.I., Reiner, A.P., Wilson, J.G., Harris, T.B., Ripatti, S, Grallert, H., Meigs, J.B, Salomaa, V., Hansen, T., van Dijk, K.W., Wareham, N.J., Grant, S.F.A., Langenberg, C., Frayling, T.M., Lindgren, C.M., Mohlke, K.L., Leibel, R.L., Loos, R.J.F., Kilpeläinen, T.O. |
| المصدر: | Diabetes 69, 2806-2818 (2020) |
| بيانات النشر: | Amer Diabetes Assoc |
| سنة النشر: | 2020 |
| المجموعة: | PuSH - Publikationsserver des Helmholtz Zentrums München |
| الوصف: | Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by admin-istering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concen-trations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0012-1797 1939-327X |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32917775; info:eu-repo/semantics/altIdentifier/wos/WOS:000594819600025; info:eu-repo/semantics/altIdentifier/isbn/0012-1797; info:eu-repo/semantics/altIdent; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=60615Test; urn:isbn:0012-1797; urn:issn:0012-1797; urn:issn:1939-327X |
| DOI: | 10.2337/db20-0070 |
| الإتاحة: | https://doi.org/10.2337/db20-0070Test https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=60615Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.19117AEF |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00121797 1939327X |
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| DOI: | 10.2337/db20-0070 |