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

TitleGenetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.
Publication TypeJournal Article
Year of Publication2020
AuthorsYaghootkar, H, Zhang, Y, Spracklen, CN, Karaderi, T, Huang, LOpal, 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, Chen, Y-DIda, Jackson, R, Jakupović, H, Jousilahti, P, Justice, AE, Kähönen, M, Kizer, JR, Kriebel, J, LeDuc, CA, Li, J, Lind, L, Luan, J'an, Mackey, D, Mangino, M, Männistö, S, Carli, JFMartin, Medina-Gómez, C, Mook-Kanamori, DO, Morris, AP, de Mutsert, R, Nauck, M, Nedeljkovic, 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, AM, 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, Wilson, JG, Harris, TB, Ripatti, S, Grallert, H, Meigs, JB, Salomaa, V, Hansen, T, van Dijk, KWillems, Wareham, NJ, Grant, SFa, Langenberg, C, Frayling, TM, Lindgren, CM, Mohlke, KL, Leibel, RL, Loos, RJf, Kilpeläinen, TO
Date Published2020 Sep 11
Abstract<p>Leptin influences food intake by informing the brain about the status of body fat stores. Rare 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 , and , and one intergenic variant near The missense variant Val94Met (rs17151919) in was common in individuals of African ancestry only and its association with lower leptin concentrations was specific to this ancestry (P=2x10, n=3,901). Using 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 leptin regulates early adiposity.</p>
Alternate JournalDiabetes
PubMed ID32917775
ePub date: