Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.
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ABSTRACT:
SUBMITTER: Justice AE
PROVIDER: S-EPMC6560635 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.
Justice Anne E AE Karaderi Tugce T Highland Heather M HM Young Kristin L KL Graff Mariaelisa M Lu Yingchang Y Turcot Valérie V Auer Paul L PL Fine Rebecca S RS Guo Xiuqing X Schurmann Claudia C Lempradl Adelheid A Marouli Eirini E Mahajan Anubha A Winkler Thomas W TW Winkler Thomas W TW Locke Adam E AE Medina-Gomez Carolina C Esko Tõnu T Vedantam Sailaja S Giri Ayush A Lo Ken Sin KS Alfred Tamuno T Mudgal Poorva P Ng Maggie C Y MCY Heard-Costa Nancy L NL Feitosa Mary F MF Manning Alisa K AK Willems Sara M SM Sivapalaratnam Suthesh S Abecasis Goncalo G Alam Dewan S DS Allison Matthew M Amouyel Philippe P Arzumanyan Zorayr Z Balkau Beverley B Bastarache Lisa L Bergmann Sven S Bielak Lawrence F LF Blüher Matthias M Boehnke Michael M Boeing Heiner H Boerwinkle Eric E Böger Carsten A CA Bork-Jensen Jette J Bottinger Erwin P EP Bowden Donald W DW Brandslund Ivan I Broer Linda L Burt Amber A AA Butterworth Adam S AS Caulfield Mark J MJ Cesana Giancarlo G Chambers John C JC Chasman Daniel I DI Chen Yii-Der Ida YI Chowdhury Rajiv R Christensen Cramer C Chu Audrey Y AY Collins Francis S FS Cook James P JP Cox Amanda J AJ Crosslin David S DS Danesh John J de Bakker Paul I W PIW Denus Simon de S Mutsert Renée de R Dedoussis George G Demerath Ellen W EW Dennis Joe G JG Denny Josh C JC Di Angelantonio Emanuele E Dörr Marcus M Drenos Fotios F Dubé Marie-Pierre MP Dunning Alison M AM Easton Douglas F DF Elliott Paul P Evangelou Evangelos E Farmaki Aliki-Eleni AE Feng Shuang S Ferrannini Ele E Ferrieres Jean J Florez Jose C JC Fornage Myriam M Fox Caroline S CS Franks Paul W PW Friedrich Nele N Gan Wei W Gandin Ilaria I Gasparini Paolo P Giedraitis Vilmantas V Girotto Giorgia G Gorski Mathias M Grallert Harald H Grarup Niels N Grove Megan L ML Gustafsson Stefan S Haessler Jeff J Hansen Torben T Hattersley Andrew T AT Hayward Caroline C Heid Iris M IM Holmen Oddgeir L OL Hovingh G Kees GK Howson Joanna M M JMM Hu Yao Y Hung Yi-Jen YJ Hveem Kristian K Ikram M Arfan MA Ingelsson Erik E Jackson Anne U AU Jarvik Gail P GP Jia Yucheng Y Jørgensen Torben T Jousilahti Pekka P Justesen Johanne M JM Kahali Bratati B Karaleftheri Maria M Kardia Sharon L R SLR Karpe Fredrik F Kee Frank F Kitajima Hidetoshi H Komulainen Pirjo P Kooner Jaspal S JS Kovacs Peter P Krämer Bernhard K BK Kuulasmaa Kari K Kuusisto Johanna J Laakso Markku M Lakka Timo A TA Lamparter David D Lange Leslie A LA Langenberg Claudia C Larson Eric B EB Lee Nanette R NR Lee Wen-Jane WJ Lehtimäki Terho T Lewis Cora E CE Li Huaixing H Li Jin J Li-Gao Ruifang R Lin Li-An LA Lin Xu X Lind Lars L Lindström Jaana J Linneberg Allan A Liu Ching-Ti CT Liu Dajiang J DJ Luan Jian'an J Lyytikäinen Leo-Pekka LP MacGregor Stuart S Mägi Reedik R Männistö Satu S Marenne Gaëlle G Marten Jonathan J Masca Nicholas G D NGD McCarthy Mark I MI Meidtner Karina K Mihailov Evelin E Moilanen Leena L Moitry Marie M Mook-Kanamori Dennis O DO Morgan Anna A Morris Andrew P AP Müller-Nurasyid Martina M Munroe Patricia B PB Narisu Narisu N Nelson Christopher P CP Neville Matt M Ntalla Ioanna I O'Connell Jeffrey R JR Owen Katharine R KR Pedersen Oluf O Peloso Gina M GM Pennell Craig E CE Perola Markus M Perry James A JA Perry John R B JRB Pers Tune H TH Ewing Ailith A Polasek Ozren O Raitakari Olli T OT Rasheed Asif A Raulerson Chelsea K CK Rauramaa Rainer R Reilly Dermot F DF Reiner Alex P AP Ridker Paul M PM Rivas Manuel A MA Robertson Neil R NR Robino Antonietta A Rudan Igor I Ruth Katherine S KS Saleheen Danish D Salomaa Veikko V Samani Nilesh J NJ Schreiner Pamela J PJ Schulze Matthias B MB Scott Robert A RA Segura-Lepe Marcelo M Sim Xueling X Slater Andrew J AJ Small Kerrin S KS Smith Blair H BH Smith Jennifer A JA Southam Lorraine L Spector Timothy D TD Speliotes Elizabeth K EK Stefansson Kari K Steinthorsdottir Valgerdur V Stirrups Kathleen E KE Strauch Konstantin K Stringham Heather M HM Stumvoll Michael M Sun Liang L Surendran Praveen P Swart Karin M A KMA Tardif Jean-Claude JC Taylor Kent D KD Teumer Alexander A Thompson Deborah J DJ Thorleifsson Gudmar G Thorsteinsdottir Unnur U Thuesen Betina H BH Tönjes Anke A Torres Mina M Tsafantakis Emmanouil E Tuomilehto Jaakko J Uitterlinden André G AG Uusitupa Matti M van Duijn Cornelia M CM Vanhala Mauno M Varma Rohit R Vermeulen Sita H SH Vestergaard Henrik H Vitart Veronique V Vogt Thomas F TF Vuckovic Dragana D Wagenknecht Lynne E LE Walker Mark M Wallentin Lars L Wang Feijie F Wang Carol A CA Wang Shuai S Wareham Nicholas J NJ Warren Helen R HR Waterworth Dawn M DM Wessel Jennifer J White Harvey D HD Willer Cristen J CJ Wilson James G JG Wood Andrew R AR Wu Ying Y Yaghootkar Hanieh H Yao Jie J Yerges-Armstrong Laura M LM Young Robin R Zeggini Eleftheria E Zhan Xiaowei X Zhang Weihua W Zhao Jing Hua JH Zhao Wei W Zheng He H Zhou Wei W Zillikens M Carola MC Rivadeneira Fernando F Borecki Ingrid B IB Pospisilik J Andrew JA Deloukas Panos P Frayling Timothy M TM Lettre Guillaume G Mohlke Karen L KL Rotter Jerome I JI Kutalik Zoltán Z Hirschhorn Joel N JN Cupples L Adrienne LA Loos Ruth J F RJF North Kari E KE Lindgren Cecilia M CM
Nature genetics 20190218 3
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 ...[more]