New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

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Lu , Y , Day , F R , Gustafsson , S , Buchkovich , M L , Na , J , Bataille , V , Cousminer , D L , Dastani , Z , Drong , A W , Esko , T , Evans , D M , Falchi , M , Feitosa , M F , Ferreira , T , Hedman , A K , Haring , R , Hysi , P G , Iles , M M , Justice , A E , Kanoni , S , Lagou , V , Li , R , Li , X , Locke , A , Lu , C , Magi , R , Perry , J R B , Pers , T H , Qi , Q , Sanna , M , Schmidt , E M , Scott , W R , Shungin , D , Teumer , A , Vinkhuyzen , A A E , Walker , R W , Westra , H-J , Zhang , M , Zhang , W , Zhao , J H , Zhu , Z , Afzal , U , Ahluwalia , T S , Bakker , S J L , Bellis , C , Bonnefond , A , Borodulin , K , Buchman , A S , Cederholm , T , Choh , A C , Choi , H J , Curran , J E , de Groot , L C P G M , De Jager , P L , Dhonukshe-Rutten , R A M , Enneman , A W , Eury , E , Evans , D S , Forsen , T , Friedrich , N , Fumeron , F , Garcia , M E , Gartner , S , Han , B-G , Havulinna , A S , Hayward , C , Hernandez , D , Hillege , H , Ittermann , T , Kent , J W , Kolcic , I , Laatikainen , T , Lahti , J , Leach , I M , Lee , C G , Lee , J-Y , Liu , T , Liu , Y , Lobbens , S , Loh , M , Lyytikainen , L-P , Medina-Gomez , C , Michaelsson , K , Nalls , M A , Nielson , C M , Oozageer , L , Pascoe , L , Paternoster , L , Polasek , O , Ripatti , S , Sarzynski , M A , Shin , C S , Narancic , N S , Spira , D , Srikanth , P , Steinhagen-Thiessen , E , Sung , Y J , Swart , K M A , Taittonen , L , Tanaka , T , Tikkanen , E , van der Velde , N , van Schoor , N M , Verweij , N , Wright , A F , Yu , L , Zmuda , J M , Pellikka , N , Forrester , T , Grarup , N , Jackson , A U , Kristiansson , K , Kuulasmaa , T , Kuusisto , J , Lichtner , P , Luan , J , Mahajan , A , Mannisto , S , Palmer , C D , Ried , J S , Scott , R A , Stancakova , A , Wagner , P J , Demirkan , A , Doring , A , Gudnason , V , Kiel , D P , Kuhnel , B , Mangino , M , Mcknight , B , Menni , C , O'Connell , J R , Oostra , B A , Shuldiner , A R , Song , K , Vandenput , L , van Duijn , C M , Vollenweider , P , White , C C , Boehnke , M , Boettcher , Y , Cooper , R S , Forouhi , N G , Gieger , C , Grallert , H , Hingorani , A , Jorgensen , T , Jousilahti , P , Kivimaki , M , Kumari , M , Laakso , M , Langenberg , C , Linneberg , A , Luke , A , Mckenzie , C A , Palotie , A , Pedersen , O , Peters , A , Strauch , K , Tayo , B O , Wareham , N J , Bennett , D A , Bertram , L , Blangero , J , Bluher , M , Bouchard , C , Campbell , H , Cho , N H , Cummings , S R , Czerwinski , S A , Demuth , I , Eckardt , R , Eriksson , J G , Ferrucci , L , Franco , O H , Froguel , P , Gansevoort , R T , Hansen , T , Harris , T B , Hastie , N , Heliovaara , M , Hofman , A , Jordan , J M , Jula , A , Kahonen , M , Kajantie , E , Knekt , P B , Koskinen , S , Kovacs , P , Lehtimaki , T , Lind , L , Liu , Y , Orwoll , E S , Osmond , C , Perola , M , Perusse , L , Raitakari , O T , Rankinen , T , Rao , D C , Rice , T K , Rivadeneira , F , Rudan , I , Salomaa , V , Sorensen , T I A , Stumvoll , M , Tonjes , A , Towne , B , Tranah , G J , Tremblay , A , Uitterlinden , A G , van der Harst , P , Vartiainen , E , Viikari , J S , Vitart , V , Vohl , M-C , Volzke , H , Walker , M , Wallaschofski , H , Wild , S , Wilson , J F , Yengo , L , Bishop , D T , Borecki , I B , Chambers , J C , Cupples , L A , Dehghan , A , Deloukas , P , Fatemifar , G , Fox , C , Furey , T S , Franke , L , Han , J , Hunter , D J , Karjalainen , J , Karpe , F , Kaplan , R C , Kooner , J S , McCarthy , M I , Murabito , J M , Morris , A P , Bishop , J A N , North , K E , Ohlsson , C , Ong , K K , Prokopenko , I , Richards , J B , Schadt , E E , Spector , T D , Widen , E , Willer , C J , Yang , J , Ingelsson , E , Mohlke , K L , Hirschhorn , J N , Pospisilik , J A , Zillikens , M C , Lindgren , C , Kilpelainen , T O & Loos , R J F 2016 , ' New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk ' , Nature Communications , vol. 7 , 10495 . https://doi.org/10.1038/ncomms10495

Title: New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
Author: Lu, Yingchang; Day, Felix R.; Gustafsson, Stefan; Buchkovich, Martin L.; Na, Jianbo; Bataille, Veronique; Cousminer, Diana L.; Dastani, Zari; Drong, Alexander W.; Esko, Tonu; Evans, David M.; Falchi, Mario; Feitosa, Mary F.; Ferreira, Teresa; Hedman, Asa K.; Haring, Robin; Hysi, Pirro G.; Iles, Mark M.; Justice, Anne E.; Kanoni, Stavroula; Lagou, Vasiliki; Li, Rui; Li, Xin; Locke, Adam; Lu, Chen; Magi, Reedik; Perry, John R. B.; Pers, Tune H.; Qi, Qibin; Sanna, Marianna; Schmidt, Ellen M.; Scott, William R.; Shungin, Dmitry; Teumer, Alexander; Vinkhuyzen, Anna A. E.; Walker, Ryan W.; Westra, Harm-Jan; Zhang, Mingfeng; Zhang, Weihua; Zhao, Jing Hua; Zhu, Zhihong; Afzal, Uzma; Ahluwalia, Tarunveer Singh; Bakker, Stephan J. L.; Bellis, Claire; Bonnefond, Amelie; Borodulin, Katja; Buchman, Aron S.; Cederholm, Tommy; Choh, Audrey C.; Choi, Hyung Jin; Curran, Joanne E.; de Groot, Lisette C. P. G. M.; De Jager, Philip L.; Dhonukshe-Rutten, Rosalie A. M.; Enneman, Anke W.; Eury, Elodie; Evans, Daniel S.; Forsen, Tom; Friedrich, Nele; Fumeron, Frederic; Garcia, Melissa E.; Gartner, Simone; Han, Bok-Ghee; Havulinna, Aki S.; Hayward, Caroline; Hernandez, Dena; Hillege, Hans; Ittermann, Till; Kent, Jack W.; Kolcic, Ivana; Laatikainen, Tiina; Lahti, Jari; Leach, Irene Mateo; Lee, Christine G.; Lee, Jong-Young; Liu, Tian; Liu, Youfang; Lobbens, Stephane; Loh, Marie; Lyytikainen, Leo-Pekka; Medina-Gomez, Carolina; Michaelsson, Karl; Nalls, Mike A.; Nielson, Carrie M.; Oozageer, Laticia; Pascoe, Laura; Paternoster, Lavinia; Polasek, Ozren; Ripatti, Samuli; Sarzynski, Mark A.; Shin, Chan Soo; Narancic, Nina Smolej; Spira, Dominik; Srikanth, Priya; Steinhagen-Thiessen, Elisabeth; Sung, Yun Ju; Swart, Karin M. A.; Taittonen, Leena; Tanaka, Toshiko; Tikkanen, Emmi; van der Velde, Nathalie; van Schoor, Natasja M.; Verweij, Niek; Wright, Alan F.; Yu, Lei; Zmuda, Joseph M.; Pellikka, Niina; Forrester, Terrence; Grarup, Niels; Jackson, Anne U.; Kristiansson, Kati; Kuulasmaa, Teemu; Kuusisto, Johanna; Lichtner, Peter; Luan, Jian'an; Mahajan, Anubha; Mannisto, Satu; Palmer, Cameron D.; Ried, Janina S.; Scott, Robert A.; Stancakova, Alena; Wagner, Peter J.; Demirkan, Ayse; Doring, Angela; Gudnason, Vilmundur; Kiel, Douglas P.; Kuhnel, Brigitte; Mangino, Massimo; Mcknight, Barbara; Menni, Cristina; O'Connell, Jeffrey R.; Oostra, Ben A.; Shuldiner, Alan R.; Song, Kijoung; Vandenput, Liesbeth; van Duijn, Cornelia M.; Vollenweider, Peter; White, Charles C.; Boehnke, Michael; Boettcher, Yvonne; Cooper, Richard S.; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Hingorani, Aroon; Jorgensen, Torben; Jousilahti, Pekka; Kivimaki, Mika; Kumari, Meena; Laakso, Markku; Langenberg, Claudia; Linneberg, Allan; Luke, Amy; Mckenzie, Colin A.; Palotie, Aarno; Pedersen, Oluf; Peters, Annette; Strauch, Konstantin; Tayo, Bamidele O.; Wareham, Nicholas J.; Bennett, David A.; Bertram, Lars; Blangero, John; Bluher, Matthias; Bouchard, Claude; Campbell, Harry; Cho, Nam H.; Cummings, Steven R.; Czerwinski, Stefan A.; Demuth, Ilja; Eckardt, Rahel; Eriksson, Johan G.; Ferrucci, Luigi; Franco, Oscar H.; Froguel, Philippe; Gansevoort, Ron T.; Hansen, Torben; Harris, Tamara B.; Hastie, Nicholas; Heliovaara, Markku; Hofman, Albert; Jordan, Joanne M.; Jula, Antti; Kahonen, Mika; Kajantie, Eero; Knekt, Paul B.; Koskinen, Seppo; Kovacs, Peter; Lehtimaki, Terho; Lind, Lars; Liu, Yongmei; Orwoll, Eric S.; Osmond, Clive; Perola, Markus; Perusse, Louis; Raitakari, Olli T.; Rankinen, Tuomo; Rao, D. C.; Rice, Treva K.; Rivadeneira, Fernando; Rudan, Igor; Salomaa, Veikko; Sorensen, Thorkild I. A.; Stumvoll, Michael; Tonjes, Anke; Towne, Bradford; Tranah, Gregory J.; Tremblay, Angelo; Uitterlinden, Andre G.; van der Harst, Pim; Vartiainen, Erkki; Viikari, Jorma S.; Vitart, Veronique; Vohl, Marie-Claude; Volzke, Henry; Walker, Mark; Wallaschofski, Henri; Wild, Sarah; Wilson, James F.; Yengo, Loic; Bishop, D. Timothy; Borecki, Ingrid B.; Chambers, John C.; Cupples, L. Adrienne; Dehghan, Abbas; Deloukas, Panos; Fatemifar, Ghazaleh; Fox, Caroline; Furey, Terrence S.; Franke, Lude; Han, Jiali; Hunter, David J.; Karjalainen, Juha; Karpe, Fredrik; Kaplan, Robert C.; Kooner, Jaspal S.; McCarthy, Mark I.; Murabito, Joanne M.; Morris, Andrew P.; Bishop, Julia A. N.; North, Kari E.; Ohlsson, Claes; Ong, Ken K.; Prokopenko, Inga; Richards, J. Brent; Schadt, Eric E.; Spector, Tim D.; Widen, Elisabeth; Willer, Cristen J.; Yang, Jian; Ingelsson, Erik; Mohlke, Karen L.; Hirschhorn, Joel N.; Pospisilik, John Andrew; Zillikens, M. Carola; Lindgren, Cecilia; Kilpelainen, Tuomas Oskari; Loos, Ruth J. F.
Contributor organization: Institute for Molecular Medicine Finland
Clinicum
Department of General Practice and Primary Health Care
Behavioural Sciences
Samuli Olli Ripatti / Principal Investigator
Department of Public Health
Aarno Palotie / Principal Investigator
Johan Eriksson / Principal Investigator
Children's Hospital
Lastentautien yksikkö
University of Helsinki
Elisabeth Ingrid Maria Widen / Principal Investigator
Biostatistics Helsinki
Quantitative Genetics
Developmental Psychology Research Group
Complex Disease Genetics
Genomics of Neurological and Neuropsychiatric Disorders
Genomic Discoveries and Clinical Translation
Date: 2016-02
Language: eng
Number of pages: 15
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/ncomms10495
URI: http://hdl.handle.net/10138/160839
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P <5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Subject: GENOME-WIDE ASSOCIATION
MASS INDEX
INSULIN-RESISTANCE
COMMON VARIANTS
GENETIC ARCHITECTURE
SUSCEPTIBILITY LOCI
IDENTIFIES COMMON
PROVIDES INSIGHTS
ENERGY-BALANCE
CUTANEOUS NEVI
3121 General medicine, internal medicine and other clinical medicine
515 Psychology
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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