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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
Kilpeläinen, Tuomas O. Martin Carli, Jayne F. Skowronski, Alicja A. Sun, Qi Kriebel, Jennifer Feitosa, Mary F. Hedman, Åsa K. Drong, Alexander W. Hayes, James E. Zhao, Jinghua H.
Kilpeläinen, Tuomas O.
Martin Carli, Jayne F.
Skowronski, Alicja A.
Sun, Qi
Kriebel, Jennifer
Feitosa, Mary F.
Hedman, Åsa K.
Drong, Alexander W.
Hayes, James E.
Zhao, Jinghua H.
Author
Kilpeläinen, Tuomas O.
Martin Carli, Jayne F.
Skowronski, Alicja A.
Sun, Qi
Kriebel, Jennifer
Feitosa, Mary F.
Hedman, Åsa K.
Drong, Alexander W.
Hayes, James E.
Zhao, Jinghua H.
Pers, Tune H.
Schick, Ursula M.
Grarup, Niels
Kutalik, Zoltán
Trompet, Stella
Mangino, Massimo
Kristiansson, Kati
Beekman, Marian
Lyytikäinen, Leo-Pekka
Eriksson, Joel
Henneman, Peter
Lahti, Jari
Tanaka, Toshiko
Luan, Jian’an
Del Greco M., Fabiola
Pasko, Dorota
Renström, Frida
Willems, Sara M.
Mahajan, Anubha
Lorentzon, Mattias
Martin Carli, Jayne F.
Skowronski, Alicja A.
Sun, Qi
Kriebel, Jennifer
Feitosa, Mary F.
Hedman, Åsa K.
Drong, Alexander W.
Hayes, James E.
Zhao, Jinghua H.
Pers, Tune H.
Schick, Ursula M.
Grarup, Niels
Kutalik, Zoltán
Trompet, Stella
Mangino, Massimo
Kristiansson, Kati
Beekman, Marian
Lyytikäinen, Leo-Pekka
Eriksson, Joel
Henneman, Peter
Lahti, Jari
Tanaka, Toshiko
Luan, Jian’an
Del Greco M., Fabiola
Pasko, Dorota
Renström, Frida
Willems, Sara M.
Mahajan, Anubha
Lorentzon, Mattias
Abstract
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Keywords
Date
2016
Type
Journal article
Journal
Nature Communications
Book
Volume
7
Issue
1
Page Range
1-14
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open
Notes
Please refer to the full article for a complete list of author names.