Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity
- Yaghootkar, H.
- Zhang, Y.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.C.
- Metz, S.
- Willems, S.M.
- Li-Gao, R.F.
- Grarup, N.
- Wang, S.
- Molnos, S.
- Sandoval-Zarate, A.A.
- Nalls, M.A.
- Lange, L.A.
- Haesser, J.
- Guo, X.Q.
- Lyytikainen, L.P.
- Feitosa, M.F.
- Sitlani, C.M.
- Venturini, C.
- Mahajan, A.
- Kacprowski, T.
- Wang, C.R.A.
- Chasman, D.I.
- Amin, N.
- Broer, L.
- Robertson, N.
- Young, K.L.
- Allison, M.
- Auer, P.L.
- Bluher, M.
- Borja, J.B.
- Bork-Jensen, J.
- Carrasquilla, G.D.
- Christofidou, P.
- Demirkan, A.
- Doege, C.A.
- Garcia, M.E.
- Graff, M.
- Guo, K.Y.
- Hakonarson, H.
- Hong, J.Y.
- Chen, Y.D.I.
- Jackson, R.
- Jakupovic, H.
- Jousilahti, P.
- Justice, A.E.
- Kahonen, M.
- Kizer, J.R.
- Kriebel, J.
- LeDuc, C.A.
- Li, J.
- Lind, L.
- Luan, J.N.
- Mackey, D.A.
- Mangino, M.
- Mannisto, S.
- Carli, J.M.F.
- Medina-Gomez, C.
- Mook-Kanamori, D.O.
- Morris, A.P.
- Mutsert, R. de
- 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.
- Duijn, C.M. van
- Ridker, P.M.
- Lye, S.
- Homuth, G.
- Ingelsson, E.
- Spector, T.D.
- McKnight, B.
- Province, M.A.
- Lehtimaki, 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.
- Dijk, K.W. van
- 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.
- Kilpelainen, T.O.
DOIAbstract
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, an...
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