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

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 × 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.

SUBMITTER: Lu Y

PROVIDER: S-EPMC4740398 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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

Lu Yingchang Y Day Felix R FR Gustafsson Stefan S Buchkovich Martin L ML Na Jianbo J Bataille Veronique V Cousminer Diana L DL Dastani Zari Z Drong Alexander W AW Esko Tõnu T Evans David M DM Falchi Mario M Feitosa Mary F MF Ferreira Teresa T Hedman Åsa K ÅK Haring Robin R Hysi Pirro G PG Iles Mark M MM Justice Anne E AE Kanoni Stavroula S Lagou Vasiliki V Li Rui R Li Xin X Locke Adam A Lu Chen C Mägi Reedik R Perry John R B JR Pers Tune H TH Qi Qibin Q Sanna Marianna M Schmidt Ellen M EM Scott William R WR Shungin Dmitry D Teumer Alexander A Vinkhuyzen Anna A E AA Walker Ryan W RW Westra Harm-Jan HJ Zhang Mingfeng M Zhang Weihua W Zhao Jing Hua JH Zhu Zhihong Z Afzal Uzma U Ahluwalia Tarunveer Singh TS Bakker Stephan J L SJ Bellis Claire C Bonnefond Amélie A Borodulin Katja K Buchman Aron S AS Cederholm Tommy T Choh Audrey C AC Choi Hyung Jin HJ Curran Joanne E JE de Groot Lisette C P G M LC De Jager Philip L PL Dhonukshe-Rutten Rosalie A M RA Enneman Anke W AW Eury Elodie E Evans Daniel S DS Forsen Tom T Friedrich Nele N Fumeron Frédéric F Garcia Melissa E ME Gärtner Simone S Han Bok-Ghee BG Havulinna Aki S AS Hayward Caroline C Hernandez Dena D Hillege Hans H Ittermann Till T Kent Jack W JW Kolcic Ivana I Laatikainen Tiina T Lahti Jari J Mateo Leach Irene I Lee Christine G CG Lee Jong-Young JY Liu Tian T Liu Youfang Y Lobbens Stéphane S Loh Marie M Lyytikäinen Leo-Pekka LP Medina-Gomez Carolina C Michaëlsson Karl K Nalls Mike A MA Nielson Carrie M CM Oozageer Laticia L Pascoe Laura L Paternoster Lavinia L Polašek Ozren O Ripatti Samuli S Sarzynski Mark A MA Shin Chan Soo CS Narančić Nina Smolej NS Spira Dominik D Srikanth Priya P Steinhagen-Thiessen Elisabeth E Sung Yun Ju YJ Swart Karin M A KM Taittonen Leena L Tanaka Toshiko T Tikkanen Emmi E van der Velde Nathalie N van Schoor Natasja M NM Verweij Niek N Wright Alan F AF Yu Lei L Zmuda Joseph M JM Eklund Niina N Forrester Terrence T Grarup Niels N Jackson Anne U AU Kristiansson Kati K Kuulasmaa Teemu T Kuusisto Johanna J Lichtner Peter P Luan Jian'an J Mahajan Anubha A Männistö Satu S Palmer Cameron D CD Ried Janina S JS Scott Robert A RA Stancáková Alena A Wagner Peter J PJ Demirkan Ayse A Döring Angela A Gudnason Vilmundur V Kiel Douglas P DP Kühnel Brigitte B Mangino Massimo M Mcknight Barbara B Menni Cristina C O'Connell Jeffrey R JR Oostra Ben A BA Shuldiner Alan R AR Song Kijoung K Vandenput Liesbeth L van Duijn Cornelia M CM Vollenweider Peter P White Charles C CC Boehnke Michael M Boettcher Yvonne Y Cooper Richard S RS Forouhi Nita G NG Gieger Christian C Grallert Harald H Hingorani Aroon A Jørgensen Torben T Jousilahti Pekka P Kivimaki Mika M Kumari Meena M Laakso Markku M Langenberg Claudia C Linneberg Allan A Luke Amy A Mckenzie Colin A CA Palotie Aarno A Pedersen Oluf O Peters Annette A Strauch Konstantin K Tayo Bamidele O BO Wareham Nicholas J NJ Bennett David A DA Bertram Lars L Blangero John J Blüher Matthias M Bouchard Claude C Campbell Harry H Cho Nam H NH Cummings Steven R SR Czerwinski Stefan A SA Demuth Ilja I Eckardt Rahel R Eriksson Johan G JG Ferrucci Luigi L Franco Oscar H OH Froguel Philippe P Gansevoort Ron T RT Hansen Torben T Harris Tamara B TB Hastie Nicholas N Heliövaara Markku M Hofman Albert A Jordan Joanne M JM Jula Antti A Kähönen Mika M Kajantie Eero E Knekt Paul B PB Koskinen Seppo S Kovacs Peter P Lehtimäki Terho T Lind Lars L Liu Yongmei Y Orwoll Eric S ES Osmond Clive C Perola Markus M Pérusse Louis L Raitakari Olli T OT Rankinen Tuomo T Rao D C DC Rice Treva K TK Rivadeneira Fernando F Rudan Igor I Salomaa Veikko V Sørensen Thorkild I A TI Stumvoll Michael M Tönjes Anke A Towne Bradford B Tranah Gregory J GJ Tremblay Angelo A Uitterlinden André G AG van der Harst Pim P Vartiainen Erkki E Viikari Jorma S JS Vitart Veronique V Vohl Marie-Claude MC Völzke Henry H Walker Mark M Wallaschofski Henri H Wild Sarah S Wilson James F JF Yengo Loïc L Bishop D Timothy DT Borecki Ingrid B IB Chambers John C JC Cupples L Adrienne LA Dehghan Abbas A Deloukas Panos P Fatemifar Ghazaleh G Fox Caroline C Furey Terrence S TS Franke Lude L Han Jiali J Hunter David J DJ Karjalainen Juha J Karpe Fredrik F Kaplan Robert C RC Kooner Jaspal S JS McCarthy Mark I MI Murabito Joanne M JM Morris Andrew P AP Bishop Julia A N JA North Kari E KE Ohlsson Claes C Ong Ken K KK Prokopenko Inga I Richards J Brent JB Schadt Eric E EE Spector Tim D TD Widén Elisabeth E Willer Cristen J CJ Yang Jian J Ingelsson Erik E Mohlke Karen L KL Hirschhorn Joel N JN Pospisilik John Andrew JA Zillikens M Carola MC Lindgren Cecilia C Kilpeläinen Tuomas Oskari TO Loos Ruth J F RJ

Nature communications 20160201

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 × 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 ...[more]

PMID: 26833246

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Project description:Objective: We aimed to assess the role of adipose tissue distribution in cardiometabolic risk (in particular insulin sensitivity) in a population of children and adolescents with obesity. Methods: In this cross-sectional study, participants were 479 children and adolescents with obesity (322 boys and 157 girls) aged 3 to 18 years attending the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China). Clinical assessments included anthropometry, body composition (DXA scans), carotid artery ultrasounds, and OGTT. Insulin sensitivity was assessed using the Matsuda index. Participants were stratified into groups by sex and pubertal stage. Key predictors were DXA-derived android-to-gynoid-fat ratio (A/G) and total body fat percentage (TBF%). Results: Irrespective of sex and pubertal stage, there was a strong association between increasing A/G (i.e., greater abdominal adiposity) and lower insulin sensitivity. In multivariable models, every 0.1 increase in A/G was associated with a reduction in insulin sensitivity in prepubertal boys [-29% (95% CI -36%, -20%); p < 0.0001], pubertal boys [-13% (95% CI -21%, -6%); p = 0.001], and pubertal girls [-16% (95% CI -24%, -6%); p = 0.002]. In contrast, TBF% was not associated with insulin sensitivity when A/G was adjusted for, irrespective of pubertal stage or sex. In addition, every 0.1 increase in A/G was associated with increased likelihood of dyslipidemia in prepubertal boys [adjusted odds ratio (aOR) 1.62 (95% CI 1.05, 2.49)], impaired glucose tolerance in pubertal boys [aOR 1.64 (95% CI 1.07, 2.51)] and pubertal girls [aOR 1.81 (95% CI 1.10, 2.98)], and odds of NAFLD in both prepubertal [aOR 2.57 (95% CI 1.56, 4.21)] and pubertal [aOR 1.69 (95% CI 1.18, 2.40)] boys. In contrast, higher TBF% was only associated with higher fasting insulin and ALT in pubertal boys, being also predictive of NAFLD in this group [aOR 1.15 per percentage point (95% CI 1.06, 1.26)], but was not associated with the likelihood of other cardiometabolic outcomes assessed in any group. Conclusions: A/G is a much stronger independent predictor of cardiometabolic risk factors in children and adolescents with obesity in China, particularly glucose metabolism.

Project description:BackgroundAccurate obesity classification is important so that appropriate intervention can be instituted to modify metabolic risk factors. Commonly utilized body mass index (BMI) and percentage body fat (PBF) are influenced by lean mass whereas fat mass index (FMI) measures only body fat. This study compares the prevalence of obesity and metabolic risk factors with FMI, BMI and PBF using DXA (dual-energy x-ray absorptiometry).Methods489 women randomly recruited from the electoral roll were stratified into 4 age groups; 40-49, 50-59, 60-69 and 70-79 years from 2000 to 2001. Clinical data and DXA body composition were obtained. Statistical analyses were performed using Medcalc v15 (Ostend, Belgium) with significance level at p = 0.05 (two-tailed).ResultsThere was higher prevalence of obesity using PBF compared to BMI and FMI (p<0.001). This difference was greater from age 50-59 (p<0.05) which may be explained by age-related lean mass loss. PBF over-classified obesity in over 35% of normal and 95% of overweight categories compared to FMI and BMI. BMI has a sensitivity of 78.9% and specificity of 98.3% for obesity using FMI as the standard. BMI under-classified obesity in the overweight category by 14.9% compared to FMI. There was no difference in diabetes, dyslipidemia, hypertension and metabolic syndrome prevalence within the BMI-obesity and FMI-obesity categories (p>0.05).ConclusionPBF classified more obesity than BMI and FMI because of its low pre-determined threshold. The greater difference with PBF compared to BMI and FMI from the 50-59 decade onwards can be attributed to age-related lean mass loss. BMI had the lowest sensitivity for obesity diagnosis. BMI under-classified obesity in the overweight category compared to FMI due to its inability to differentiate lean mass. However, there was no significant difference in the prevalence of metabolic risk factors between BMI and FMI-obesity categories indicating that fat location may influence metabolic dysregulation.

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

Publications

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

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