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

  1. Kilpeläinen, Tuomas O.
  2. Carli, Jayne F. Martin
  3. Skowronski, Alicja A.
  4. Sun, Qi
  5. Kriebel, Jennifer
  6. Feitosa, Mary F
  7. Hedman, Åsa K.
  8. Drong, Alexander W.
  9. Hayes, James E.
  10. Zhao, Jinghua
  11. Pers, Tune H.
  12. Schick, Ursula
  13. Grarup, Niels
  14. Kutalik, Zoltán
  15. Trompet, Stella
  16. Mangino, Massimo
  17. Kristiansson, Kati
  18. Beekman, Marian
  19. Lyytikäinen, Leo-Pekka
  20. Eriksson, Joel
  21. Henneman, Peter
  22. Lahti, Jari
  23. Tanaka, Toshiko
  24. Luan, Jian’an
  25. Greco M, Fabiola Del
  26. Pasko, Dorota
  27. Renström, Frida
  28. Willems, Sara M.
  29. Mahajan, Anubha
  30. Rose, Lynda M.
  31. Guo, Xiuqing
  32. Liu, Yongmei
  33. Kleber, Marcus E.
  34. Pérusse, Louis
  35. Gaunt, Tom
  36. Ahluwalia, Tarunveer S.
  37. Ju Sung, Yun
  38. Ramos, Yolande F.
  39. Amin, Najaf
  40. Amuzu, Antoinette
  41. Barroso, Inês
  42. Bellis, Claire
  43. Blangero, John
  44. Buckley, Brendan M.
  45. Böhringer, Stefan
  46. I Chen, Yii-Der
  47. de Craen, Anton J. N.
  48. Crosslin, David R.
  49. Dale, Caroline E.
  50. Dastani, Zari
  51. Day, Felix R.
  52. Deelen, Joris
  53. Delgado, Graciela E.
  54. Demirkan, Ayse
  55. Finucane, Francis M.
  56. Ford, Ian
  57. Garcia, Melissa E.
  58. Gieger, Christian
  59. Gustafsson, Stefan
  60. Hallmans, Göran
  61. Hankinson, Susan E.
  62. Havulinna, Aki S
  63. Herder, Christian ORCID logo
  64. Hernandez, Dena
  65. Hicks, Andrew A.
  66. Hunter, David J.
  67. Illig, Thomas
  68. Ingelsson, Erik
  69. Ioan-Facsinay, Andreea
  70. Jansson, John-Olov
  71. Jenny, Nancy S.
  72. Jørgensen, Marit E.
  73. Jørgensen, Torben
  74. Karlsson, Magnus
  75. Koenig, Wolfgang
  76. Kraft, Peter
  77. Kwekkeboom, Joanneke
  78. Laatikainen, Tiina
  79. Ladwig, Karl-Heinz
  80. LeDuc, Charles A.
  81. Lowe, Gordon
  82. Lu, Yingchang
  83. Marques-Vidal, Pedro
  84. Meisinger, Christa
  85. Menni, Cristina
  86. Morris, Andrew P.
  87. Myers, Richard H.
  88. Männistö, Satu
  89. Nalls, Mike A.
  90. Paternoster, Lavinia
  91. Peters, Annette
  92. Pradhan, Aruna D.
  93. Rankinen, Tuomo
  94. Rasmussen-Torvik, Laura J.
  95. Rathmann, Wolfgang
  96. Rice, Treva K.
  97. Brent Richards, J
  98. Ridker, Paul M.
  99. Sattar, Naveed
  100. Savage, David B.
  101. Söderberg, Stefan
  102. Timpson, Nicholas J.
  103. Vandenput, Liesbeth
  104. van Heemst, Diana
  105. Uh, Hae-Won
  106. Vohl, Marie-Claude
  107. Walker, Mark
  108. Wichmann, Heinz-Erich
  109. Widén, Elisabeth
  110. Wood, Andrew R.
  111. Yao, Jie
  112. Zeller, Tanja
  113. Zhang, Yiying
  114. Meulenbelt, Ingrid
  115. Kloppenburg, Margreet
  116. Astrup, Arne
  117. Sørensen, Thorkild I. A.
  118. Sarzynski, Mark A.
  119. Rao, D. C.
  120. Jousilahti, Pekka
  121. Vartiainen, Erkki
  122. Hofman, Albert
  123. Rivadeneira, Fernando
  124. Uitterlinden, André G.
  125. Kajantie, Eero
  126. Osmond, Clive
  127. Palotie, Aarno
  128. Eriksson, Johan G.
  129. Heliövaara, Markku
  130. Knekt, Paul B.
  131. Koskinen, Seppo
  132. Jula, Antti
  133. Perola, Markus
  134. Huupponen, Risto K.
  135. Viikari, Jorma S.
  136. Kähönen, Mika
  137. Lehtimäki, Terho
  138. Raitakari, Olli T.
  139. Mellström, Dan
  140. Lorentzon, Mattias
  141. Casas, Juan P.
  142. Bandinelli, Stefanie
  143. März, Winfried
  144. Isaacs, Aaron
  145. van Dijk, Ko W.
  146. van Duijn, Cornelia M.
  147. Harris, Tamara B.
  148. Bouchard, Claude
  149. Allison, Matthew A.
  150. Chasman, Daniel I.
  151. Ohlsson, Claes
  152. Lind, Lars
  153. Scott, Robert A.
  154. Langenberg, Claudia
  155. Wareham, Nicholas J.
  156. Ferrucci, Luigi
  157. Frayling, Timothy M.
  158. Pramstaller, Peter P.
  159. Borecki, Ingrid B.
  160. Waterworth, Dawn M.
  161. Bergmann, Sven
  162. Waeber, Gérard
  163. Vollenweider, Peter
  164. Vestergaard, Henrik
  165. Hansen, Torben
  166. Pedersen, Oluf
  167. Hu, Frank B.
  168. Eline Slagboom, P
  169. Grallert, Harald
  170. Spector, Tim D.
  171. Jukema, J.W.
  172. Klein, Robert J.
  173. Schadt, Erik E
  174. Franks, Paul W.
  175. Lindgren, Cecilia M.
  176. Leibel, Rudolph L.
  177. Loos, Ruth J. F.

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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.pdf 693,64KB
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1000 Titel
  • Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
1000 Autor/in
  1. Kilpeläinen, Tuomas O. |
  2. Carli, Jayne F. Martin |
  3. Skowronski, Alicja A. |
  4. Sun, Qi |
  5. Kriebel, Jennifer |
  6. Feitosa, Mary F |
  7. Hedman, Åsa K. |
  8. Drong, Alexander W. |
  9. Hayes, James E. |
  10. Zhao, Jinghua |
  11. Pers, Tune H. |
  12. Schick, Ursula |
  13. Grarup, Niels |
  14. Kutalik, Zoltán |
  15. Trompet, Stella |
  16. Mangino, Massimo |
  17. Kristiansson, Kati |
  18. Beekman, Marian |
  19. Lyytikäinen, Leo-Pekka |
  20. Eriksson, Joel |
  21. Henneman, Peter |
  22. Lahti, Jari |
  23. Tanaka, Toshiko |
  24. Luan, Jian’an |
  25. Greco M, Fabiola Del |
  26. Pasko, Dorota |
  27. Renström, Frida |
  28. Willems, Sara M. |
  29. Mahajan, Anubha |
  30. Rose, Lynda M. |
  31. Guo, Xiuqing |
  32. Liu, Yongmei |
  33. Kleber, Marcus E. |
  34. Pérusse, Louis |
  35. Gaunt, Tom |
  36. Ahluwalia, Tarunveer S. |
  37. Ju Sung, Yun |
  38. Ramos, Yolande F. |
  39. Amin, Najaf |
  40. Amuzu, Antoinette |
  41. Barroso, Inês |
  42. Bellis, Claire |
  43. Blangero, John |
  44. Buckley, Brendan M. |
  45. Böhringer, Stefan |
  46. I Chen, Yii-Der |
  47. de Craen, Anton J. N. |
  48. Crosslin, David R. |
  49. Dale, Caroline E. |
  50. Dastani, Zari |
  51. Day, Felix R. |
  52. Deelen, Joris |
  53. Delgado, Graciela E. |
  54. Demirkan, Ayse |
  55. Finucane, Francis M. |
  56. Ford, Ian |
  57. Garcia, Melissa E. |
  58. Gieger, Christian |
  59. Gustafsson, Stefan |
  60. Hallmans, Göran |
  61. Hankinson, Susan E. |
  62. Havulinna, Aki S |
  63. Herder, Christian |
  64. Hernandez, Dena |
  65. Hicks, Andrew A. |
  66. Hunter, David J. |
  67. Illig, Thomas |
  68. Ingelsson, Erik |
  69. Ioan-Facsinay, Andreea |
  70. Jansson, John-Olov |
  71. Jenny, Nancy S. |
  72. Jørgensen, Marit E. |
  73. Jørgensen, Torben |
  74. Karlsson, Magnus |
  75. Koenig, Wolfgang |
  76. Kraft, Peter |
  77. Kwekkeboom, Joanneke |
  78. Laatikainen, Tiina |
  79. Ladwig, Karl-Heinz |
  80. LeDuc, Charles A. |
  81. Lowe, Gordon |
  82. Lu, Yingchang |
  83. Marques-Vidal, Pedro |
  84. Meisinger, Christa |
  85. Menni, Cristina |
  86. Morris, Andrew P. |
  87. Myers, Richard H. |
  88. Männistö, Satu |
  89. Nalls, Mike A. |
  90. Paternoster, Lavinia |
  91. Peters, Annette |
  92. Pradhan, Aruna D. |
  93. Rankinen, Tuomo |
  94. Rasmussen-Torvik, Laura J. |
  95. Rathmann, Wolfgang |
  96. Rice, Treva K. |
  97. Brent Richards, J |
  98. Ridker, Paul M. |
  99. Sattar, Naveed |
  100. Savage, David B. |
  101. Söderberg, Stefan |
  102. Timpson, Nicholas J. |
  103. Vandenput, Liesbeth |
  104. van Heemst, Diana |
  105. Uh, Hae-Won |
  106. Vohl, Marie-Claude |
  107. Walker, Mark |
  108. Wichmann, Heinz-Erich |
  109. Widén, Elisabeth |
  110. Wood, Andrew R. |
  111. Yao, Jie |
  112. Zeller, Tanja |
  113. Zhang, Yiying |
  114. Meulenbelt, Ingrid |
  115. Kloppenburg, Margreet |
  116. Astrup, Arne |
  117. Sørensen, Thorkild I. A. |
  118. Sarzynski, Mark A. |
  119. Rao, D. C. |
  120. Jousilahti, Pekka |
  121. Vartiainen, Erkki |
  122. Hofman, Albert |
  123. Rivadeneira, Fernando |
  124. Uitterlinden, André G. |
  125. Kajantie, Eero |
  126. Osmond, Clive |
  127. Palotie, Aarno |
  128. Eriksson, Johan G. |
  129. Heliövaara, Markku |
  130. Knekt, Paul B. |
  131. Koskinen, Seppo |
  132. Jula, Antti |
  133. Perola, Markus |
  134. Huupponen, Risto K. |
  135. Viikari, Jorma S. |
  136. Kähönen, Mika |
  137. Lehtimäki, Terho |
  138. Raitakari, Olli T. |
  139. Mellström, Dan |
  140. Lorentzon, Mattias |
  141. Casas, Juan P. |
  142. Bandinelli, Stefanie |
  143. März, Winfried |
  144. Isaacs, Aaron |
  145. van Dijk, Ko W. |
  146. van Duijn, Cornelia M. |
  147. Harris, Tamara B. |
  148. Bouchard, Claude |
  149. Allison, Matthew A. |
  150. Chasman, Daniel I. |
  151. Ohlsson, Claes |
  152. Lind, Lars |
  153. Scott, Robert A. |
  154. Langenberg, Claudia |
  155. Wareham, Nicholas J. |
  156. Ferrucci, Luigi |
  157. Frayling, Timothy M. |
  158. Pramstaller, Peter P. |
  159. Borecki, Ingrid B. |
  160. Waterworth, Dawn M. |
  161. Bergmann, Sven |
  162. Waeber, Gérard |
  163. Vollenweider, Peter |
  164. Vestergaard, Henrik |
  165. Hansen, Torben |
  166. Pedersen, Oluf |
  167. Hu, Frank B. |
  168. Eline Slagboom, P |
  169. Grallert, Harald |
  170. Spector, Tim D. |
  171. Jukema, J.W. |
  172. Klein, Robert J. |
  173. Schadt, Erik E |
  174. Franks, Paul W. |
  175. Lindgren, Cecilia M. |
  176. Leibel, Rudolph L. |
  177. Loos, Ruth J. F. |
1000 Erscheinungsjahr 2016
1000 LeibnizOpen
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-02-01
1000 Erschienen in
1000 Quellenangabe
  • 7:10494
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/ncomms10494 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740377/ |
1000 Ergänzendes Material
  • https://www.nature.com/articles/ncomms10494#supplementary-information |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Fachgruppe
  1. Medizin |
  2. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. Academy of Finland
  2. Ahokas Foundation
  3. ALF/LUA
  4. Amgen
  5. Augustinus Foundation
  6. Becket Foundation
  7. Bristol-Myers Squibb
  8. British Heart Foundation
  9. Canadian Institutes of Health Research
  10. Centre for Medical Systems Biology
  11. Danish Centre for Health Technology Assessment
  12. Danish Council for Independent Research
  13. Danish Diabetes Association
  14. Danish Heart Foundation
  15. Danish Pharmaceutical Association
  16. Danish Research Council
  17. Department of Health Policy Research Programme
  18. Diabetes UK
  19. Donald W. Reynolds Foundation
  20. Dutch Arthritis Association
  21. Dutch government
  22. Emil Aaltonen Foundation
  23. Erasmus MC
  24. Erasmus University
  25. European Commission
  26. European Regional Development Fund
  27. EUROSPAN
  28. Faculty of Biology and Medicine of Lausanne
  29. Finnish Centre for Pensions
  30. Finnish Cultural Foundation
  31. Finnish Diabetes Research Society
  32. Finnish Foundation of Cardiovascular Research
  33. Finnish Foundation for Pediatric Research
  34. Finnish National Institute for Health and Welfare
  35. Finnish Special Governmental Subsidy for Health Sciences
  36. Finska Läkaresällskapet
  37. Folkhälsan Research Foundation
  38. Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
  39. German Center for Diabetes Research (DZD)
  40. German Federal Ministry of Education and Research
  41. GlaxoSmithKline
  42. Göran Gustafsson Foundation
  43. Heart Foundation of Northern Sweden
  44. Helmholtz Zentrum München
  45. Ib Henriksen Foundation
  46. Innovation-Oriented Research Program on Genomics
  47. Italian Ministry of Health
  48. John W. Barton Sr. Chair in Genetics and Nutrition
  49. Juho Vainio Foundation
  50. King’s College London
  51. Knut and Alice Wallenberg Foundation
  52. Kuopio, Tampere and Turku University Hospital Medical Funds
  53. Leiden University Medical Centre
  54. Li Ka Shing Foundation
  55. Liv och Hälsa
  56. Local Government Pensions Institution
  57. Ludwig-Maximilians-Universität
  58. Lundbeck Foundation
  59. Lundberg Foundation
  60. Medical Research Council
  61. Medical Research Council-GlaxoSmithKline pilot programme grant
  62. Ministry of Education, Culture and Science of the Netherlands
  63. Ministry of health, Welfare and Sports of the Netherlands
  64. Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano
  65. Danish Ministry of Internal Affairs and Health
  66. Munich Center of Health Sciences
  67. Municipality of Rotterdam
  68. National Cancer Institute
  69. National Eye Institute
  70. National Institute on Aging
  71. National Institute for Health Research
  72. National Institutes of Health
  73. Netherlands Brain Foundation (HersenStichting Nederland)
  74. Netherlands Consortium for Healthy Aging
  75. Netherlands Genomics Initiative
  76. Netherlands Heart Foundation
  77. Netherlands Organization for Scientific Research
  78. Netherlands Organization for the Health Research and Development
  79. National Heart, Lung, and Blood Institute
  80. National Health Service Foundation Trust
  81. National Institutes of Diabetes and Digestive and Kidney Diseases
  82. Novo Nordisk
  83. Novo Nordisk Foundation
  84. New York Obesity Nutrition Research Center
  85. Orion-Farmos Research Foundation
  86. Pfizer Inc.
  87. Paavo Nurmi Foundation
  88. Påhlssons Foundation
  89. Research Foundation of Copenhagen County
  90. Roche Pharmaceuticals
  91. Research Institute for Diseases in the Elderly
  92. Samfundet Folkhälsan
  93. Signe and Ane Gyllenberg Foundation
  94. Sigrid Jusélius Foundation
  95. Social Insurance Institution of Finland
  96. South Tyrolean Sparkasse Foundation
  97. Swedish Diabetes Association
  98. Swedish Diabetes Foundation
  99. Swedish Foundation for Strategic Research
  100. Swedish Heart-Lung Foundation
  101. Swedish Research Council
  102. Swiss Institute of Bioinformatics
  103. Swiss National Science Foundation
  104. Tampere Tuberculosis Foundation
  105. Torsten and Ragnar Söderberg’s Foundation
  106. Umeå University
  107. Unilever Colworth
  108. Wellcome Trust
  109. Wissenschaftsoffensive TMO
  110. Yrjö Jahnsson Foundation
1000 Fördernummer
  1. 41071; 117787; 118065; 121584; 124282; 126925; 129494; 129322; 129378; 130326; 134309; 134791; 136895; 139635; 250207; 263836; 286284 ; 263924
  2. -
  3. -
  4. -
  5. -
  6. -
  7. -
  8. PG/13/66/30442 ; PG/07/131/24254
  9. FRCN-CCT-83028
  10. -
  11. -
  12. DFF-1333-00124 ; DFF-1331-00730B
  13. -
  14. -
  15. -
  16. -
  17. 90049
  18. -
  19. -
  20. DAA 2010_017
  21. NWO 184.021.007
  22. -
  23. -
  24. -
  25. FP6-LSHG-CT-2006-018947; FP6-LSHG-CT-2006-01947; HEALTH-F2-2008-201865-GEFOS; FP7-201668; FP7-223004; FP7-259679; FP7-305739 ; FP7-IDEAS-ERC-323195
  26. -
  27. -
  28. -
  29. -
  30. -
  31. -
  32. -
  33. -
  34. -
  35. -
  36. -
  37. -
  38. -
  39. -
  40. -
  41. -
  42. -
  43. -
  44. -
  45. -
  46. SenterNovem IGE05007
  47. ICS110.1; RF97.71
  48. -
  49. -
  50. -
  51. -
  52. X51001; 9M048; 9N035
  53. -
  54. -
  55. -
  56. -
  57. -
  58. -
  59. -
  60. MC_U106179471; MC_UU_12013/3; MC_UU_12013/8
  61. G0701863
  62. -
  63. -
  64. -
  65. -
  66. -
  67. -
  68. CA047988
  69. -
  70. N01AG62101; N01AG62103; N01AG62106; 1R01AG032098-01A1; 263MD9164 ; 263MD821336
  71. -
  72. DK52431; HG004399; HG004446; CA087969; CA055075; DK058845; CA65725; CA49449; CA67262; CA50385 ; UO1CA098233
  73. -
  74. 050-060-810
  75. -
  76. 2001 D 032
  77. 175-010-2005-011; 904-61-095; 911-03-012; 911-03-016; 917-66-344 ; 911-03-012
  78. -
  79. 5R01HL068891; 5R01HL087700; R01HL117078; HHSN26800625226C; HHSN268200782096C; HL-043851; HL-045670; HL080467; N01-HC95159; N01-HC-95160; N01-HC-95161; N01-HC-95162; N01-HC-95163; N01-HC-95164; N01-HC-95165; N01-HC-95166; N01-HC-95167; N01-HC-95168; N01-HC-95169; N02-HL-64278; N01-HC-65226; R01-HL-071051; R01-HL-071205; R01-HL-071250; R01-HL-071251; R01-HL-071252; R01-HL-071258; R01-HL-071259; R01-HL-088451; R00-HL-098459; U01-HG007033; UL1-RR-24156; UL1-RR-25005; UL1-TR-000040 ; UL1-TR-001079
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  81. 1R01DK080015; R01DK089256; 5R01DK068336; 5R01DK075681 ; 5R01DK07568102
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  108. WT064890; WT089062; WT090532; WT098017; WT098051; WT091551; 081917/Z/07/Z ; 086596/Z/08/Z; 90532
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  108. Centre for Human Genetics core funding
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1000 Dateien
  1. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6407884.rdf
1000 Erstellt am 2018-04-26T09:00:39.351+0200
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1000 Zuletzt bearbeitet Thu Jan 30 21:27:22 CET 2020
1000 Objekt bearb. Tue Jul 03 09:20:37 CEST 2018
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1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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