PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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.*

Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity.

Diabetes 69, 2806-2818 (2020)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
7.720
1.882
6
6
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Plasma Leptin; Obesity; Loci; Rare; Variants; Metaanalysis; Expenditure; Homeostasis; Deficiency
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 69, Issue: 12, Pages: 2806-2818 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
POF-Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-002
G-504100-001
Grants NHGRI NIH
Johnson Johnson
National Institute on Aging, National Institutes of Health
Data Tecnica International
DOI 10.2337/db20-0070
WOS ID WOS:000594819600025
Scopus ID 85096618864
PubMed ID 32917775
Erfassungsdatum 2020-12-16
[➜Report correction]