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Bispebjerg Hospital - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

DOI

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  • Hanieh Yaghootkar
  • Yiying Zhang
  • Cassandra N. Spracklen
  • Tugce Karaderi
  • Lam Opal Huang
  • Jonathan Bradfield
  • Claudia Schurmann
  • Rebecca S. Fine
  • Michael H. Preuss
  • Zoltan Kutalik
  • Laura B. L. Wittemans
  • Yingchang Lu
  • Sophia Metz
  • Sara M. Willems
  • Ruifang Li-Gao
  • Niels Grarup
  • Shuai Wang
  • Sophie Molnos
  • America A. Sandoval-Zarate
  • Mike A. Nalls
  • Leslie A. Lange
  • Jeffrey Haesser
  • Xiuqing Guo
  • Leo-Pekka Lyytikainen
  • Mary F. Feitosa
  • Colleen M. Sitlani
  • Cristina Venturini
  • Anubha Mahajan
  • Tim Kacprowski
  • Carol A. Wang
  • Daniel I. Chasman
  • Najaf Amin
  • Linda Broer
  • Neil Robertson
  • Kristin L. Young
  • Matthew Allison
  • Paul L. Auer
  • Matthias Bluher
  • Judith B. Borja
  • Jette Bork-Jensen
  • German D. Carrasquilla
  • Paraskevi Christofidou
  • Ayse Demirkan
  • Claudia A. Doege
  • Melissa E. Garcia
  • Mariaelisa Graff
  • Kaiying Guo
  • Hakon Hakonarson
  • Jaeyoung Hong
  • Yii-Der Ida Chen
  • Rebecca Jackson
  • Hermina Jakupovic
  • Pekka Jousilahti
  • Anne E. Justice
  • Mika Kahonen
  • Jorge R. Kizer
  • Jennifer Kriebel
  • Charles A. LeDuc
  • Jin Li
  • Lars Lind
  • Jian'an Luan
  • David A. Mackey
  • Massimo Mangino
  • Satu Mannisto
  • Jayne F. Martin Carli
  • Carolina Medina-Gomez
  • Dennis O. Mook-Kanamori
  • Andrew P. Morris
  • Renee de Mutsert
  • Matthias Nauck
  • Ivana Prokic
  • Craig E. Pennell
  • Arund D. Pradhan
  • Bruce M. Psaty
  • Olli T. Raitakari
  • Robert A. Scott
  • Tea Skaaby
  • Konstantin Strauch
  • Kent D. Taylor
  • Alexander Teumer
  • Andre G. Uitterlinden
  • Ying Wu
  • Jie Yao
  • Mark Walker
  • Kari E. North
  • Peter Kovacs
  • M. Arfan Ikram
  • Cornelia M. van Duijn
  • Paul M. Ridker
  • Stephen Lye
  • Georg Homuth
  • Erik Ingelsson
  • Tim D. Spector
  • Barbara McKnight
  • Michael A. Province
  • Terho Lehtimaki
  • Linda S. Adair
  • Jerome I. Rotter
  • Alexander P. Reiner
  • James G. Wilson
  • Tamara B. Harris
  • Samuli Ripatti
  • Harald Grallert
  • James B. Meigs
  • Veikko Salomaa
  • Torben Hansen
  • Ko Willems van Dijk
  • Nicholas J. Wareham
  • Struan F. A. Grant
  • Claudia Langenberg
  • Timothy M. Frayling
  • Cecilia M. Lindgren
  • Karen L. Mohlke
  • Rudolph L. Leibel
  • Ruth J. F. Loos
  • Tuomas O. Kilpelainen
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind69
Udgave nummer12
Sider (fra-til)2806-2818
Antal sider13
ISSN0012-1797
DOI
StatusUdgivet - dec. 2020

Bibliografisk note

© 2020 by the American Diabetes Association.

ID: 60966028