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

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Serval ID
serval:BIB_99AF60202BCB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
UNIL/CHUV
Title
Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.
Journal
Diabetes
Author(s)
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 LBL, 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., Ida Chen Y.D., 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., Martin Carli J.F., 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., 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., Willems van Dijk K., Wareham N.J., Grant SFA, Langenberg C., Frayling T.M., Lindgren C.M., Mohlke K.L., Leibel R.L., Loos RJF, Kilpeläinen T.O.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Publication state
Published
Issued date
12/2020
Peer-reviewed
Oui
Volume
69
Number
12
Pages
2806-2818
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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 <sup>-16</sup> , 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.
Keywords
Adiposity/genetics, Continental Population Groups/genetics, Gene Expression Regulation, Developmental, Genetic Variation, Genotype, Humans, Leptin/blood, Leptin/chemistry, Leptin/genetics, Leptin/metabolism, Models, Molecular, Protein Conformation
OAI-PMH
oai:serval.unil.ch:BIB_99AF60202BCB
DOI
10.2337/db20-0070
Pubmed
32917775
Web of science
000594819600025
Create date
19/09/2020 12:57
Last modification date
17/02/2021 6:27
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