Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

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  • Additional Information
    • Source:
      Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: In Process; Core Clinical (AIM); MEDLINE
    • Publication Information:
      Publication: Alexandria, VA : American Diabetes Association
      Original Publication: [New York, American Diabetes Association]
    • Abstract:
      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 administering 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 concentrations. 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.
      (© 2020 by the American Diabetes Association.)
    • Publication Date:
      Date Created: 20200912 Latest Revision: 20201123
    • Publication Date:
      20201123
    • Accession Number:
      10.2337/db20-0070
    • Accession Number:
      32917775
  • Citations
    • ABNT:
      YAGHOOTKAR, H. et al. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. Diabetes, [s. l.], v. 69, n. 12, p. 2806–2818, 2020. DOI 10.2337/db20-0070. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=mnh&AN=32917775. Acesso em: 26 nov. 2020.
    • AMA:
      Yaghootkar H, Zhang Y, Spracklen CN, et al. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. Diabetes. 2020;69(12):2806-2818. doi:10.2337/db20-0070
    • APA:
      Yaghootkar, H., Zhang, Y., Spracklen, C. N., Karaderi, T., Huang, L. O., Bradfield, J., 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., … Kilpeläinen, T. O. (2020). Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. Diabetes, 69(12), 2806–2818. https://doi.org/10.2337/db20-0070
    • Chicago/Turabian: Author-Date:
      Yaghootkar, Hanieh, Yiying Zhang, Cassandra N Spracklen, Tugce Karaderi, Lam Opal Huang, Jonathan Bradfield, Claudia Schurmann, et al. 2020. “Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.” Diabetes 69 (12): 2806–18. doi:10.2337/db20-0070.
    • Harvard:
      Yaghootkar, H. et al. (2020) ‘Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity’, Diabetes, 69(12), pp. 2806–2818. doi: 10.2337/db20-0070.
    • Harvard: Australian:
      Yaghootkar, H, Zhang, Y, Spracklen, CN, Karaderi, T, Huang, LO, Bradfield, J, Schurmann, C, Fine, RS, Preuss, MH, Kutalik, Z, Wittemans, LBL, Lu, Y, Metz, S, Willems, SM, Li-Gao, R, Grarup, N, Wang, S, Molnos, S, Sandoval-Zárate, AA, Nalls, MA, Lange, LA, Haesser, J, Guo, X, Lyytikäinen, L-P, Feitosa, MF, Sitlani, CM, Venturini, C, Mahajan, A, Kacprowski, T, Wang, CA, Chasman, DI, Amin, N, Broer, L, Robertson, N, Young, KL, Allison, M, Auer, PL, Blüher, M, Borja, JB, Bork-Jensen, J, Carrasquilla, GD, Christofidou, P, Demirkan, A, Doege, CA, Garcia, ME, Graff, M, Guo, K, Hakonarson, H, Hong, J, Ida Chen, Y-D, Jackson, R, Jakupović, H, Jousilahti, P, Justice, AE, Kähönen, M, Kizer, JR, Kriebel, J, LeDuc, CA, Li, J, Lind, L, Luan, J, Mackey, DA, Mangino, M, Männistö, S, Martin Carli, JF, Medina-Gomez, C, Mook-Kanamori, DO, Morris, AP, de Mutsert, R, Nauck, M, Prokic, I, Pennell, CE, Pradhan, AD, Psaty, BM, Raitakari, OT, Scott, RA, Skaaby, T, Strauch, K, Taylor, KD, Teumer, A, Uitterlinden, AG, Wu, Y, Yao, J, Walker, M, North, KE, Kovacs, P, Ikram, MA, van Duijn, CM, Ridker, PM, Lye, S, Homuth, G, Ingelsson, E, Spector, TD, McKnight, B, Province, MA, Lehtimäki, T, Adair, LS, Rotter, JI, Reiner, AP, et al. 2020, ‘Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity’, Diabetes, vol. 69, no. 12, pp. 2806–2818, viewed 26 November 2020, .
    • MLA:
      Yaghootkar, Hanieh, et al. “Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.” Diabetes, vol. 69, no. 12, Dec. 2020, pp. 2806–2818. EBSCOhost, doi:10.2337/db20-0070.
    • Chicago/Turabian: Humanities:
      Yaghootkar, Hanieh, Yiying Zhang, Cassandra N Spracklen, Tugce Karaderi, Lam Opal Huang, Jonathan Bradfield, Claudia Schurmann, et al. “Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.” Diabetes 69, no. 12 (December 2020): 2806–18. doi:10.2337/db20-0070.
    • Vancouver/ICMJE:
      Yaghootkar H, Zhang Y, Spracklen CN, Karaderi T, Huang LO, Bradfield J, et al. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. Diabetes [Internet]. 2020 Dec [cited 2020 Nov 26];69(12):2806–18. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=mnh&AN=32917775