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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Justice, Anne E. (author)
University of North Carolina,Geisinger Health System
Karaderi, Tugce (author)
Highland, Heather M. (author)
show more...
Lind, Lars (author)
Uppsala universitet,Klinisk epidemiologi
Graff, Mariaelisa (author)
Lu, Yingchang (author)
Turcot, Valerie (author)
Auer, Paul L. (author)
Fine, Rebecca S. (author)
Guo, Xiuqing (author)
Schurmann, Claudia (author)
Lempradl, Adelheid (author)
Marouli, Eirini (author)
Mahajan, Anubha (author)
Winkler, Thomas W. (author)
Locke, Adam E. (author)
Medina-Gomez, Carolina (author)
Esko, Tonu (author)
Vedantam, Sailaja (author)
Giri, Ayush (author)
Lo, Ken Sin (author)
Alfred, Tamuno (author)
Mudgal, Poorva (author)
Ng, Maggie C. Y. (author)
Heard-Costa, Nancy L. (author)
Feitosa, Mary F. (author)
Manning, Alisa K. (author)
Willems, Sara M. (author)
Sivapalaratnam, Suthesh (author)
Abecasis, Goncalo (author)
Alam, Dewan S. (author)
Allison, Matthew (author)
Amouyel, Philippe (author)
Arzumanyanm, Zorayr (author)
Balkau, Beverley (author)
Bastarache, Lisa (author)
Bergmann, Sven (author)
Bielak, Lawrence F. (author)
Blueher, Matthias (author)
Boehnke, Michael (author)
Boeing, Heiner (author)
Boerwinkle, Eric (author)
Boeger, Carsten A. (author)
Bork-Jensen, Jette (author)
Bottinger, Erwin P. (author)
Bowden, Donald W. (author)
Brandslund, Ivan (author)
Broer, Linda (author)
Burt, Amber A. (author)
Butterworth, Adam S. (author)
Caulfield, Markj (author)
Cesana, Giancarlo (author)
Chambers, John C. (author)
Chasman, Daniel, I (author)
Chen, Yii-Der Ida (author)
Chowdhury, Rajiv (author)
Christensen, Cramer (author)
Chu, Audreyy (author)
Collins, Francis S. (author)
Cook, James P. (author)
Cox, Amanda J. (author)
Crosslin, David S. (author)
Danesh, John (author)
de Bakker, Paul I. W. (author)
de Denus, Simon (author)
de Mutsert, Renee (author)
Dedoussis, George (author)
Demerath, Ellen W. (author)
Dennis, Joe G. (author)
Denny, Josh C. (author)
Di Angelantonio, Emanuele (author)
Doerr, Marcus (author)
Drenos, Fotios (author)
Dube, Marie-Pierre (author)
Dunning, Alison M. (author)
Easton, Douglas F. (author)
Elliott, Paul (author)
Evangelou, Evangelos (author)
University of North Carolina
Farmaki, Aliki-Eleni (author)
Feng, Shuang (author)
Ferrannini, Ele (author)
Ferrieres, Jean (author)
Florez, Jose C. (author)
Fornage, Myriam (author)
Fox, Caroline S. (author)
Franks, Paul W. (author)
Umeå University,Lund University,Lunds universitet,Umeå universitet,Avdelningen för medicin,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Friedrich, Nele (author)
Gan, Wei (author)
Gandin, Ilaria (author)
Gasparini, Paolo (author)
Giedraitis, Vilmantas (author)
Uppsala universitet,Geriatrik
Girotto, Giorgia (author)
Gorski, Mathias (author)
Grallert, Harald (author)
Grarup, Niels (author)
Groves, Megan L. (author)
Gustafsson, Stefan (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi
Haessler, Jeff (author)
Hansen, Torben (author)
Hattersley, Andrew T. (author)
Hayward, Caroline (author)
Heid, Iris M. (author)
Holmen, Oddgeir L. (author)
Hovingh, G. Kees (author)
Howson, Joanna M. M. (author)
Hu, Yao (author)
Hung, Yi-Jen (author)
Hveem, Kristian (author)
Ikram, M. Arfan (author)
Ingelsson, Erik, 1975- (author)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA
Jackson, Anne U. (author)
Jarvik, Gail P. (author)
Jia, Yucheng (author)
Jorgensen, Torben (author)
Jousilahti, Pekka (author)
Justesen, Johanne M. (author)
Kahali, Bratati (author)
Karaleftheri, Maria (author)
Kardia, Sharon L. R. (author)
Karpe, Fredrik (author)
Kee, Frank (author)
Kitajima, Hidetoshi (author)
Komulainen, Pirjo (author)
Kooner, Jaspal S. (author)
Kovacs, Peter (author)
Kraemer, Bernhard K. (author)
Kuulasmaa, Kari (author)
Kuusisto, Johanna (author)
Laakso, Markku (author)
Lakka, Timo A. (author)
Lamparter, David (author)
La Nge, Leslie A. (author)
Langenberg, Claudia (author)
Larson, Eric B. (author)
Lee, Nanette R. (author)
Lee, Wen-Jane (author)
Lehtimaeki, Terho (author)
Lewis, Cora E. (author)
Li, Huaixing (author)
Li, Jin (author)
Lin, Li-An (author)
Lin, Xu (author)
Lind, Lars (author)
Lindstroem, Jaana (author)
Linneberg, Allan (author)
Liu, Ching-Ti (author)
Liu, Dajiang J. (author)
Luan, Jian'an (author)
Lyytikainen, Leo-Pekka (author)
MacGregor, Stuart (author)
Magi, Reedik (author)
Mannisto, Satu (author)
Marenne, Gaelle (author)
Marten, Jonathan (author)
Mascal, Nicholas G. D. (author)
McCarthy, Mark, I (author)
Meidtner, Karina (author)
Mihailov, Evelin (author)
Moilanen, Leena (author)
Moitry, Marie (author)
University of Oxford
Mook-Kanamori, Dennis O. (author)
Morgan, Anna (author)
Morris, Andrew P. (author)
Mueller-Nurasyid, Martina (author)
Munroe, Patricia B. (author)
Narisu, Narisu (author)
Nelson, Christopher P. (author)
Neville, Matt (author)
Ntalla, Ioanna (author)
Owen, Katharine R. (author)
Pedersen, Oluf (author)
Peloso, Gina M. (author)
Pennell, Craig E. (author)
Perola, Markus (author)
James, A. (author)
Perry, John R. B. (author)
Pers, Tune H. (author)
Ewing, Ailith (author)
Polasek, Ozren (author)
Rasheed, Asif (author)
Raulerson, Chelsea K. (author)
Rauramaa, Rainer (author)
Reilly, Dermot F. (author)
Reiner, Alex P. (author)
Ridker, Paul M. (author)
Rivas, Manuel A. (author)
Robertson, Neil R. (author)
Robino, Antonietta (author)
Rudan, Igor (author)
Ruth, Katherine S. (author)
Saleheen, Danish (author)
Salomaa, Veikko (author)
Samani, Nilesh J. (author)
Schreiner, Pamela J. (author)
Schulze, Matthias B. (author)
Scott, Robert A. (author)
Segura-Lepe, Marcelo (author)
Sim, Xueling (author)
Slater, Andrew J. (author)
Small, Kerrin S. (author)
Smith, Blair H. (author)
Smith, Jennifer A. (author)
Southam, Lorraine (author)
Spector, Timothy D. (author)
Speliotes, Elizabeth K. (author)
Stefansson, Kari (author)
Steinthorsdottir, Valgerdur (author)
Stirrups, Kathleen E. (author)
Strauch, Konstantin (author)
Stringham, Heather M. (author)
Stumvoll, Michael (author)
Sun, Liang (author)
Surendran, Praveen (author)
Swart, Karin M. A. (author)
Tardif, Jean-Claude (author)
Taylor, Kent D. (author)
Teumer, Alexander (author)
Thompson, Deborah J. (author)
Thorleifsson, Gudmar (author)
Thorsteinsdottir, Unnur (author)
Thuesen, Betina H. (author)
Toenjes, Anke (author)
Torres, Mina (author)
Tsafantakis, Emmanouil (author)
Tuomilehto, Jaakko (author)
Uitterlinden, Andre G. (author)
Uusitupa, Matti (author)
van Duijn, Cornelia M. (author)
Vanhala, Mauno (author)
Varma, Rohit (author)
Vermeulen, Sita H. (author)
Vestergaard, Henrik (author)
Vitart, Veronique (author)
Vogt, Thomas F. (author)
Vuckovic, Dragana (author)
Wagenknecht, Lynne E. (author)
Walker, Mark (author)
Wallentin, Lars, 1943- (author)
Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
Wang, Feijie (author)
Wang, Carol A. (author)
Wang, Shuai (author)
Wareham, N. Icholas J. (author)
Warren, Helen R. (author)
Waterworth, Dawn M. (author)
Wessel, Jennifer (author)
White, Harvey D. (author)
Willer, Cristen J. (author)
Wilson, James G. (author)
Wood, Andrew R. (author)
Wu, Ying (author)
Yaghootkar, Hanieh (author)
Yao, Jie (author)
Verges-Armstrong, Laura M. (author)
Young, Robin (author)
Zeggini, Eleftheria (author)
Zhan, Xiaowei (author)
Zhang, Weihua (author)
Zhao, Jing Hua (author)
Zhao, Wei (author)
Zheng, He (author)
Zhou, Wei (author)
Zillikens, M. Carola (author)
Rivadeneira, Fernando (author)
Borecki, Ingrid B. (author)
Pospisilik, J. Andrew (author)
Deloukas, Panos (author)
Frayling, Timothy M. (author)
Lettre, Guillaume (author)
Mohlke, Karen L. (author)
Rotter, Jerome, I (author)
Kutalik, Zoltan (author)
Hirschhorn, Joel N. (author)
Cupples, L. Adrienne (author)
Loos, Ruth J. F. (author)
North, Kari E. (author)
Lindgren, Cecilia M. (author)
O'Connell, Jeffrey R. (author)
Raitakari, Olli T. (author)
Lange, Leslie A. (author)
Uitterlinden, Andr G. (author)
Grove, Megan L. (author)
Masca, Nicholas G. D. (author)
Luan, Jianan (author)
Wareham, Nicholas J. (author)
Esko, Tnu (author)
De Bakker, Paul Iw (author)
Caulfield, Mark J. (author)
Mller-Nurasyid, Martina (author)
show less...
 (creator_code:org_t)
et al 
2019-02-18
2019
English.
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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ref (subject category)
art (subject category)

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By the author/editor
Justice, Anne E.
Karaderi, Tugce
Highland, Heathe ...
Lind, Lars
Graff, Mariaelis ...
Lu, Yingchang
show more...
Turcot, Valerie
Auer, Paul L.
Fine, Rebecca S.
Guo, Xiuqing
Schurmann, Claud ...
Lempradl, Adelhe ...
Marouli, Eirini
Mahajan, Anubha
Winkler, Thomas ...
Locke, Adam E.
Medina-Gomez, Ca ...
Esko, Tonu
Vedantam, Sailaj ...
Giri, Ayush
Lo, Ken Sin
Alfred, Tamuno
Mudgal, Poorva
Ng, Maggie C. Y.
Heard-Costa, Nan ...
Feitosa, Mary F.
Manning, Alisa K ...
Willems, Sara M.
Sivapalaratnam, ...
Abecasis, Goncal ...
Alam, Dewan S.
Allison, Matthew
Amouyel, Philipp ...
Arzumanyanm, Zor ...
Balkau, Beverley
Bastarache, Lisa
Bergmann, Sven
Bielak, Lawrence ...
Blueher, Matthia ...
Boehnke, Michael
Boeing, Heiner
Boerwinkle, Eric
Boeger, Carsten ...
Bork-Jensen, Jet ...
Bottinger, Erwin ...
Bowden, Donald W ...
Brandslund, Ivan
Broer, Linda
Burt, Amber A.
Butterworth, Ada ...
Caulfield, Markj
Cesana, Giancarl ...
Chambers, John C ...
Chasman, Daniel, ...
Chen, Yii-Der Id ...
Chowdhury, Rajiv
Christensen, Cra ...
Chu, Audreyy
Collins, Francis ...
Cook, James P.
Cox, Amanda J.
Crosslin, David ...
Danesh, John
de Bakker, Paul ...
de Denus, Simon
de Mutsert, Rene ...
Dedoussis, Georg ...
Demerath, Ellen ...
Dennis, Joe G.
Denny, Josh C.
Di Angelantonio, ...
Doerr, Marcus
Drenos, Fotios
Dube, Marie-Pier ...
Dunning, Alison ...
Easton, Douglas ...
Elliott, Paul
Evangelou, Evang ...
Farmaki, Aliki-E ...
Feng, Shuang
Ferrannini, Ele
Ferrieres, Jean
Florez, Jose C.
Fornage, Myriam
Fox, Caroline S.
Franks, Paul W.
Friedrich, Nele
Gan, Wei
Gandin, Ilaria
Gasparini, Paolo
Giedraitis, Vilm ...
Girotto, Giorgia
Gorski, Mathias
Grallert, Harald
Grarup, Niels
Groves, Megan L.
Gustafsson, Stef ...
Haessler, Jeff
Hansen, Torben
Hattersley, Andr ...
Hayward, Carolin ...
Heid, Iris M.
Holmen, Oddgeir ...
Hovingh, G. Kees
Howson, Joanna M ...
Hu, Yao
Hung, Yi-Jen
Hveem, Kristian
Ikram, M. Arfan
Ingelsson, Erik, ...
Jackson, Anne U.
Jarvik, Gail P.
Jia, Yucheng
Jorgensen, Torbe ...
Jousilahti, Pekk ...
Justesen, Johann ...
Kahali, Bratati
Karaleftheri, Ma ...
Kardia, Sharon L ...
Karpe, Fredrik
Kee, Frank
Kitajima, Hideto ...
Komulainen, Pirj ...
Kooner, Jaspal S ...
Kovacs, Peter
Kraemer, Bernhar ...
Kuulasmaa, Kari
Kuusisto, Johann ...
Laakso, Markku
Lakka, Timo A.
Lamparter, David
La Nge, Leslie A ...
Langenberg, Clau ...
Larson, Eric B.
Lee, Nanette R.
Lee, Wen-Jane
Lehtimaeki, Terh ...
Lewis, Cora E.
Li, Huaixing
Li, Jin
Lin, Li-An
Lin, Xu
Lindstroem, Jaan ...
Linneberg, Allan
Liu, Ching-Ti
Liu, Dajiang J.
Luan, Jian'an
Lyytikainen, Leo ...
MacGregor, Stuar ...
Magi, Reedik
Mannisto, Satu
Marenne, Gaelle
Marten, Jonathan
Mascal, Nicholas ...
McCarthy, Mark, ...
Meidtner, Karina
Mihailov, Evelin
Moilanen, Leena
Moitry, Marie
Mook-Kanamori, D ...
Morgan, Anna
Morris, Andrew P ...
Mueller-Nurasyid ...
Munroe, Patricia ...
Narisu, Narisu
Nelson, Christop ...
Neville, Matt
Ntalla, Ioanna
Owen, Katharine ...
Pedersen, Oluf
Peloso, Gina M.
Pennell, Craig E ...
Perola, Markus
James, A.
Perry, John R. B ...
Pers, Tune H.
Ewing, Ailith
Polasek, Ozren
Rasheed, Asif
Raulerson, Chels ...
Rauramaa, Rainer
Reilly, Dermot F ...
Reiner, Alex P.
Ridker, Paul M.
Rivas, Manuel A.
Robertson, Neil ...
Robino, Antoniet ...
Rudan, Igor
Ruth, Katherine ...
Saleheen, Danish
Salomaa, Veikko
Samani, Nilesh J ...
Schreiner, Pamel ...
Schulze, Matthia ...
Scott, Robert A.
Segura-Lepe, Mar ...
Sim, Xueling
Slater, Andrew J ...
Small, Kerrin S.
Smith, Blair H.
Smith, Jennifer ...
Southam, Lorrain ...
Spector, Timothy ...
Speliotes, Eliza ...
Stefansson, Kari
Steinthorsdottir ...
Stirrups, Kathle ...
Strauch, Konstan ...
Stringham, Heath ...
Stumvoll, Michae ...
Sun, Liang
Surendran, Prave ...
Swart, Karin M. ...
Tardif, Jean-Cla ...
Taylor, Kent D.
Teumer, Alexande ...
Thompson, Debora ...
Thorleifsson, Gu ...
Thorsteinsdottir ...
Thuesen, Betina ...
Toenjes, Anke
Torres, Mina
Tsafantakis, Emm ...
Tuomilehto, Jaak ...
Uitterlinden, An ...
Uusitupa, Matti
van Duijn, Corne ...
Vanhala, Mauno
Varma, Rohit
Vermeulen, Sita ...
Vestergaard, Hen ...
Vitart, Veroniqu ...
Vogt, Thomas F.
Vuckovic, Dragan ...
Wagenknecht, Lyn ...
Walker, Mark
Wallentin, Lars, ...
Wang, Feijie
Wang, Carol A.
Wang, Shuai
Wareham, N. Icho ...
Warren, Helen R.
Waterworth, Dawn ...
Wessel, Jennifer
White, Harvey D.
Willer, Cristen ...
Wilson, James G.
Wood, Andrew R.
Wu, Ying
Yaghootkar, Hani ...
Yao, Jie
Verges-Armstrong ...
Young, Robin
Zeggini, Elefthe ...
Zhan, Xiaowei
Zhang, Weihua
Zhao, Jing Hua
Zhao, Wei
Zheng, He
Zhou, Wei
Zillikens, M. Ca ...
Rivadeneira, Fer ...
Borecki, Ingrid ...
Pospisilik, J. A ...
Deloukas, Panos
Frayling, Timoth ...
Lettre, Guillaum ...
Mohlke, Karen L.
Rotter, Jerome, ...
Kutalik, Zoltan
Hirschhorn, Joel ...
Cupples, L. Adri ...
Loos, Ruth J. F.
North, Kari E.
Lindgren, Cecili ...
O'Connell, Jeffr ...
Raitakari, Olli ...
Lange, Leslie A.
Uitterlinden, An ...
Grove, Megan L.
Masca, Nicholas ...
Luan, Jianan
Wareham, Nichola ...
Esko, Tnu
De Bakker, Paul ...
Caulfield, Mark ...
Mller-Nurasyid, ...
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
Articles in the publication
Nature Genetics
By the university
Umeå University
Uppsala University
Lund University

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