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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Overview of attention for article published in Nature Communications, February 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (94th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (64th percentile)

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2 news outlets
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25 X users
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4 Facebook pages
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1 Google+ user

Citations

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157 Dimensions

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294 Mendeley
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3 CiteULike
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Title
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
Published in
Nature Communications, February 2016
DOI 10.1038/ncomms10494
Pubmed ID
Authors

Tuomas O. Kilpeläinen, Jayne F. Martin Carli, Alicja A. Skowronski, Qi Sun, Jennifer Kriebel, Mary F Feitosa, Åsa K. Hedman, Alexander W. Drong, James E. Hayes, Jinghua Zhao, Tune H. Pers, Ursula Schick, Niels Grarup, Zoltán Kutalik, Stella Trompet, Massimo Mangino, Kati Kristiansson, Marian Beekman, Leo-Pekka Lyytikäinen, Joel Eriksson, Peter Henneman, Jari Lahti, Toshiko Tanaka, Jian’an Luan, Fabiola Del Greco M, Dorota Pasko, Frida Renström, Sara M. Willems, Anubha Mahajan, Lynda M. Rose, Xiuqing Guo, Yongmei Liu, Marcus E. Kleber, Louis Pérusse, Tom Gaunt, Tarunveer S. Ahluwalia, Yun Ju Sung, Yolande F. Ramos, Najaf Amin, Antoinette Amuzu, Inês Barroso, Claire Bellis, John Blangero, Brendan M. Buckley, Stefan Böhringer, Yii-Der I Chen, Anton J. N. de Craen, David R. Crosslin, Caroline E. Dale, Zari Dastani, Felix R. Day, Joris Deelen, Graciela E. Delgado, Ayse Demirkan, Francis M. Finucane, Ian Ford, Melissa E. Garcia, Christian Gieger, Stefan Gustafsson, Göran Hallmans, Susan E. Hankinson, Aki S Havulinna, Christian Herder, Dena Hernandez, Andrew A. Hicks, David J. Hunter, Thomas Illig, Erik Ingelsson, Andreea Ioan-Facsinay, John-Olov Jansson, Nancy S. Jenny, Marit E. Jørgensen, Torben Jørgensen, Magnus Karlsson, Wolfgang Koenig, Peter Kraft, Joanneke Kwekkeboom, Tiina Laatikainen, Karl-Heinz Ladwig, Charles A. LeDuc, Gordon Lowe, Yingchang Lu, Pedro Marques-Vidal, Christa Meisinger, Cristina Menni, Andrew P. Morris, Richard H. Myers, Satu Männistö, Mike A. Nalls, Lavinia Paternoster, Annette Peters, Aruna D. Pradhan, Tuomo Rankinen, Laura J. Rasmussen-Torvik, Wolfgang Rathmann, Treva K. Rice, J Brent Richards, Paul M. Ridker, Naveed Sattar, David B. Savage, Stefan Söderberg, Nicholas J. Timpson, Liesbeth Vandenput, Diana van Heemst, Hae-Won Uh, Marie-Claude Vohl, Mark Walker, Heinz-Erich Wichmann, Elisabeth Widén, Andrew R. Wood, Jie Yao, Tanja Zeller, Yiying Zhang, Ingrid Meulenbelt, Margreet Kloppenburg, Arne Astrup, Thorkild I. A. Sørensen, Mark A. Sarzynski, D. C. Rao, Pekka Jousilahti, Erkki Vartiainen, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Eero Kajantie, Clive Osmond, Aarno Palotie, Johan G. Eriksson, Markku Heliövaara, Paul B. Knekt, Seppo Koskinen, Antti Jula, Markus Perola, Risto K. Huupponen, Jorma S. Viikari, Mika Kähönen, Terho Lehtimäki, Olli T. Raitakari, Dan Mellström, Mattias Lorentzon, Juan P. Casas, Stefanie Bandinelli, Winfried März, Aaron Isaacs, Ko W. van Dijk, Cornelia M. van Duijn, Tamara B. Harris, Claude Bouchard, Matthew A. Allison, Daniel I. Chasman, Claes Ohlsson, Lars Lind, Robert A. Scott, Claudia Langenberg, Nicholas J. Wareham, Luigi Ferrucci, Timothy M. Frayling, Peter P. Pramstaller, Ingrid B. Borecki, Dawn M. Waterworth, Sven Bergmann, Gérard Waeber, Peter Vollenweider, Henrik Vestergaard, Torben Hansen, Oluf Pedersen, Frank B. Hu, P Eline Slagboom, Harald Grallert, Tim D. Spector, J.W. Jukema, Robert J. Klein, Erik E Schadt, Paul W. Franks, Cecilia M. Lindgren, Rudolph L. Leibel, Ruth J. F. Loos

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.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 294 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 <1%
Netherlands 2 <1%
United States 1 <1%
Finland 1 <1%
Unknown 288 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 56 19%
Student > Ph. D. Student 41 14%
Student > Master 32 11%
Student > Bachelor 31 11%
Professor 19 6%
Other 61 21%
Unknown 54 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 52 18%
Medicine and Dentistry 51 17%
Agricultural and Biological Sciences 36 12%
Psychology 13 4%
Nursing and Health Professions 12 4%
Other 54 18%
Unknown 76 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 31. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 September 2016.
All research outputs
#1,223,603
of 24,792,414 outputs
Outputs from Nature Communications
#18,665
of 53,949 outputs
Outputs of similar age
#22,220
of 408,228 outputs
Outputs of similar age from Nature Communications
#263
of 747 outputs
Altmetric has tracked 24,792,414 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 53,949 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 56.0. This one has gotten more attention than average, scoring higher than 65% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 408,228 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 747 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.