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

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Kilpeläinen, Tuomas O (author)

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

Article/chapterEnglish2016

Publisher, publication year, extent ...

2016-02-01
Springer Science and Business Media LLC,2016
electronicrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-275673
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-275673URI
https://doi.org/10.1038/ncomms10494DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-118403URI
https://lup.lub.lu.se/record/8829803URI
https://gup.ub.gu.se/publication/243492URI

Supplementary language notes

Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Health Sciences Public Health, Global Health, Social Medicine and Epidemiology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
NATURVETENSKAP Biologi Genetik hsv//swe
NATURAL SCIENCES Biological Sciences Genetics hsv//eng
adipose tissue; animal tissue; Article; birth weight; body mass; controlled study; explant; female; follow up; gene locus; genetic association; genetic trait; human; major clinical study; male; meta analysis (topic); mouse; nonhuman; obesity

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Carli, Jayne F Martin (author)
Skowronski, Alicja A (author)
Sun, Qi (author)
Kriebel, Jennifer (author)
Feitosa, Mary F (author)
Hedman, Åsa KUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ashed124 (author)
Drong, Alexander W (author)
Hayes, James E (author)
Zhao, Jinghua (author)
Pers, Tune H (author)
Schick, Ursula (author)
Grarup, Niels (author)
Kutalik, Zoltán (author)
Trompet, Stella (author)
Mangino, Massimo (author)
Kristiansson, Kati (author)
Beekman, Marian (author)
Lyytikäinen, Leo-Pekka (author)
Eriksson, JoelGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xerjoe (author)
Henneman, Peter (author)
Lahti, Jari (author)
Tanaka, Toshiko (author)
Luan, Jian'an (author)
Greco M, Fabiola Del (author)
Pasko, Dorota (author)
Renström, FridaUmeå University,Lund University,Lunds universitet,Umeå universitet,Enheten för biobanksforskning,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö 20502, Sweden,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-frm (author)
Willems, Sara M (author)
Mahajan, Anubha (author)
Rose, Lynda M (author)
Guo, Xiuqing (author)
Liu, Yongmei (author)
Kleber, Marcus E (author)
Pérusse, Louis (author)
Gaunt, Tom (author)
Söderberg, StefanUmeå universitet,Kardiologi(Swepub:umu)stso0001 (author)
Ju Sung, Yun (author)
Ramos, Yolande F (author)
Amin, Najaf (author)
Amuzu, Antoinette (author)
Barroso, Inês (author)
Bellis, Claire (author)
Blangero, John (author)
Buckley, Brendan M (author)
Böhringer, Stefan (author)
I Chen, Yii-Der (author)
de Craen, Anton J N (author)
Crosslin, David R (author)
Dale, Caroline E (author)
Dastani, Zari (author)
Day, Felix R (author)
Deelen, Joris (author)
Delgado, Graciela E (author)
Demirkan, Ayse (author)
Finucane, Francis M (author)
Ford, Ian (author)
Garcia, Melissa E (author)
Gieger, Christian (author)
Gustafsson, StefanUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)stegu732 (author)
Hallmans, GöranUmeå universitet,Näringsforskning,Enheten för biobanksforskning (author)
Hankinson, Susan E (author)
Havulinna, Aki S (author)
Herder, Christian (author)
Hernandez, Dena (author)
Hicks, Andrew A (author)
Hunter, David J (author)
Illig, Thomas (author)
Ingelsson, ErikUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ering425 (author)
Ioan-Facsinay, Andreea (author)
Jansson, John-Olov,1954Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xjanjo (author)
Jenny, Nancy S (author)
Jørgensen, Marit E (author)
Jørgensen, Torben (author)
Karlsson, MagnusLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)orto-mka (author)
Koenig, Wolfgang (author)
Kraft, Peter (author)
Kwekkeboom, Joanneke (author)
Laatikainen, Tiina (author)
Ladwig, Karl-Heinz (author)
LeDuc, Charles A (author)
Lowe, Gordon (author)
Lu, Yingchang (author)
Marques-Vidal, Pedro (author)
Meisinger, Christa (author)
Menni, Cristina (author)
Morris, Andrew P (author)
Myers, Richard H (author)
Männistö, Satu (author)
Nalls, Mike A (author)
Paternoster, Lavinia (author)
Peters, Annette (author)
Pradhan, Aruna D (author)
Rankinen, Tuomo (author)
Rasmussen-Torvik, Laura J (author)
Rathmann, Wolfgang (author)
Rice, Treva K (author)
Brent Richards, J (author)
Ridker, Paul M (author)
Sattar, Naveed (author)
Savage, David B (author)
Söderberg, Stefan (author)
Timpson, Nicholas J (author)
Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xvanli (author)
van Heemst, Diana (author)
Uh, Hae-Won (author)
Vohl, Marie-Claude (author)
Walker, Mark (author)
Wichmann, Heinz-Erich (author)
Widén, Elisabeth (author)
Wood, Andrew R (author)
Yao, Jie (author)
Zeller, Tanja (author)
Zhang, Yiying (author)
Meulenbelt, Ingrid (author)
Kloppenburg, Margreet (author)
Astrup, Arne (author)
Sørensen, Thorkild I A (author)
Sarzynski, Mark A (author)
Rao, D C (author)
Jousilahti, Pekka (author)
Vartiainen, Erkki (author)
Hofman, Albert (author)
Rivadeneira, Fernando (author)
Uitterlinden, André G (author)
Kajantie, Eero (author)
Osmond, Clive (author)
Palotie, Aarno (author)
Eriksson, Johan G (author)
Heliövaara, Markku (author)
Knekt, Paul B (author)
Koskinen, Seppo (author)
Jula, Antti (author)
Perola, Markus (author)
Huupponen, Risto K (author)
Viikari, Jorma S (author)
Kähönen, Mika (author)
Lehtimäki, Terho (author)
Raitakari, Olli T (author)
Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmelda (author)
Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlomat (author)
Casas, Juan P (author)
Bandinelli, Stefanie (author)
März, Winfried (author)
Isaacs, Aaron (author)
van Dijk, Ko W (author)
van Duijn, Cornelia M (author)
Harris, Tamara B (author)
Bouchard, Claude (author)
Allison, Matthew A (author)
Chasman, Daniel I (author)
Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl (author)
Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
Scott, Robert A (author)
Langenberg, Claudia (author)
Wareham, Nicholas J (author)
Ferrucci, Luigi (author)
Frayling, Timothy M (author)
Pramstaller, Peter P (author)
Borecki, Ingrid B (author)
Waterworth, Dawn M (author)
Bergmann, Sven (author)
Waeber, Gérard (author)
Vollenweider, Peter (author)
Vestergaard, Henrik (author)
Hansen, Torben (author)
Pedersen, Oluf (author)
Hu, Frank B (author)
Eline Slagboom, P (author)
Grallert, Harald (author)
Spector, Tim D (author)
Jukema, J W (author)
Klein, Robert J (author)
Schadt, Erik E (author)
Franks, Paul W.Umeå University,Lund University,Lunds universitet,Umeå universitet,Medicin,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachussetts 02115, USA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö 20502, Sweden,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf (author)
Lindgren, Cecilia M (author)
Leibel, Rudolph L (author)
Loos, Ruth J F (author)
Uppsala universitetMolekylär epidemiologi (creator_code:org_t)

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By the author/editor: Kilpeläinen, Tuo ...; Carli, Jayne F M ...; Skowronski, Alic ...; Sun, Qi; Kriebel, Jennife ...; Feitosa, Mary F; show more...; Hedman, Åsa K; Drong, Alexander ...; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Ka ...; Beekman, Marian; Lyytikäinen, Leo ...; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola ...; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Söderberg, Stefa ...; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinett ...; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan ...; Böhringer, Stefa ...; I Chen, Yii-Der; de Craen, Anton ...; Crosslin, David ...; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciel ...; Demirkan, Ayse; Finucane, Franci ...; Ford, Ian; Garcia, Melissa ...; Gieger, Christia ...; Gustafsson, Stef ...; Hallmans, Göran; Hankinson, Susan ...; Havulinna, Aki S; Herder, Christia ...; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, A ...; Jansson, John-Ol ...; Jenny, Nancy S; Jørgensen, Marit ...; Jørgensen, Torbe ...; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joan ...; Laatikainen, Tii ...; Ladwig, Karl-Hei ...; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, P ...; Meisinger, Chris ...; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lav ...; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik ...; Rathmann, Wolfga ...; Rice, Treva K; Brent Richards, ...; Ridker, Paul M; Sattar, Naveed; Savage, David B; Timpson, Nichola ...; Vandenput, Liesb ...; van Heemst, Dian ...; Uh, Hae-Won; Vohl, Marie-Clau ...; Walker, Mark; Wichmann, Heinz- ...; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingr ...; Kloppenburg, Mar ...; Astrup, Arne; Sørensen, Thorki ...; Sarzynski, Mark ...; Rao, D C; Jousilahti, Pekk ...; Vartiainen, Erkk ...; Hofman, Albert; Rivadeneira, Fer ...; Uitterlinden, An ...; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan ...; Heliövaara, Mark ...; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto ...; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli ...; Mellström, Dan, ...; Lorentzon, Matti ...; Casas, Juan P; Bandinelli, Stef ...; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Corne ...; Harris, Tamara B; Bouchard, Claude; Allison, Matthew ...; Chasman, Daniel ...; Ohlsson, Claes, ...; Lind, Lars; Scott, Robert A; Langenberg, Clau ...; Wareham, Nichola ...; Ferrucci, Luigi; Frayling, Timoth ...; Pramstaller, Pet ...; Borecki, Ingrid ...; Waterworth, Dawn ...; Bergmann, Sven; Waeber, Gérard; Vollenweider, Pe ...; Vestergaard, Hen ...; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, ...; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecili ...; Leibel, Rudolph ...; Loos, Ruth J F; show less...

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